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The outreach quarterly connecting science with society

ISSN 2517-7028
ISSUE 104

FEATURING RESEARCH FROM:


North Carolina State University, American Chemical Society, University of Glasgow, Lancaster University,
University of Birmingham and King’s College London, Heriot-Watt University, University of Notre Dame,
University of Minnesota, Arizona State University, School of Electrical and Electronic Engineering at Manchester
University, Canadian Public Health Association, Dalhousie University, University of Alberta, The Rockefeller
University, University of Toronto, Oregon State University, University of Alaska Fairbanks, Des Moines University,
Research Features 3
Smithsonian Astrophysical Observatory, British Antarctic Survey, Louisiana State University, Christian-Albrechts-
University, University of California.
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RESEARCH OUTREACH ISSUE 104


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ISSUE 104

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ENGAGE Across the globe, a wealth of valuable research is conducted
every day. Sadly though, this vital work isn’t always visible
FEATURING RESEARCH FROM:
North Carolina State University, American Chemical Society, University of Glasgow, Lancaster University,
University of Birmingham and King’s College London, Heriot-Watt University, University of Notre Dame,
University of Minnesota, Arizona State University, School of Electrical and Electronic Engineering at Manchester
University, Canadian Public Health Association, Dalhousie University, University of Alberta, The Rockefeller
University, University of Toronto, Oregon State University, University of Alaska Fairbanks, Des Moines University,
Research Features 3
Smithsonian Astrophysical Observatory, British Antarctic Survey, Louisiana State University, Christian-Albrechts-
University, University of California.

to the public.

Dr Donna Nelson of the American Chemical Society has


THIS ISSUE
made it her mission to change the public perception and Published by:
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Bad, Dr Nelson’s commitment to increased awareness of the simon@researchoutreach.org
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As Chair of the Canadian Public Health Association (CPHA), Dr audience@researchoutreach.org
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Professor Mike Meredith is tackling a significant global tobias@researchoutreach.org
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completely barrier-free publishing portal. We have teams to maximise their exposure is the use of Survey, he investigates the role oceans play in slowing climate James Harwood
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www.researchoutreach.org 3
CONTENTS
06 UNDERSTANDING
WHY MATERIALS FAIL
Dr Srikanth Patala
The impact of ‘grain boundaries’
on the structural integrity of
many materials.

10
62
ACS: TAKING CHEMISTRY TO
HOLLYWOOD
Dr Donna Nelson
Aiming to change the public
perception and appreciation of
science, particularly chemistry.

14 DESIGNING CATALYSTS
BIT BY BIT
Prof Roy L. Johnston and Dr
Francesca Baletto
Using novel computational
approaches to understand and
design nanocatalysts. 78 34 66
18 CLEANER PATHWAYS
TO CHEMICAL SYNTHESIS
VIA NEW GENERATION
CATALYSTS 30 IN SEARCH OF 42 CPHA: THE HEART OF 54 RAISING ANTIBODIES 70 EXTINCT GIANTS, A NEW 86 ENERGISING LIFE ON EARTH:
Professor Mark Keane SUPERMASSIVE BLACK HOLE CANADIAN PUBLIC HEALTH AGAINST PROTEIN WOLF AND THE KEY TO THE THIRD WAY
Developing methods for clean FEEDBACK Dr Suzanne Jackson COMPLEXES UNDERSTANDING CLIMATE Dr Kirstin Gutekunst
chemical production from Professor Evan Scannapieco Advocating for public health at Dr John LaCava CHANGE Discovering a new pathway of
renewable feedstocks. Investigating why the largest all levels of government. Identifying interactions between Dr Julie Meachen carbohydrate breakdown in
galaxies in the universe have transcription factors and other Re-opening excavations at cyanobacteria and plants.
22 SEEING THE STRUCTURES become dormant. 46 A NEW CLASS OF ANTIBIOTIC macromolecules. Natural Trap Cave (NTC) in
OF MOLECULES: INSIGHTS DRUGS North America. 90 UNLOCKING THE CHEMICAL
FROM NMR AND INDUSTRY 34 OFFSHORE WIND POWER’S Professor Chris McMaster 58 IMPAIRED THEORY OF SECRETS OF MICROBIAL
Professor Anthony Serianni BIG BREAK Developing these drugs could MIND ASSOCIATED WITH 74 THE SUN’S CROWNING CONVERSATIONS
Experimental approaches to Professor Mike Barnes save lives and reduce healthcare VERY PRETERM BIRTH – GLORY: OBSERVING THE Dr Matt Traxler
understand and identify the 3D Designing novel circuit breakers costs. AN INVISIBLE HANDICAP CORONA Developing a method to study
structures of compunds. for offshore power networks. Dr Margot Taylor Edward E. DeLuca microbes under their natural
50 PREVENTING AND TREATING Investigating how very preterm Exploring the outer atmosphere conditions.
26 CONFIGURING NEW BONDS 38 MAKING THE INTERNET A COMPLICATIONS OF HEART (VPT) birth impacts social of the Sun during the Great
BETWEEN FIRST-ROW SAFER PLACE FAILURE AND FABRY DISEASE cognitive function. American Eclipse. 94 COMMUNICATION
TRANSITION METALS Dimitrios Pezaros & David Dr Gavin Y Oudit Why science must combat


Professor Connie Lu
Synthesising the first mixed-
Hutchison
Developing new technologies to
Developing ground-breaking
therapies to treat genetic and
62 SUPERVOLCANO
FORENSICS: UNRAVELLING
78 BAS: INVESTIGATING ICY
WATERS WITH BOATY
sensationalism

metal complex containing only fight against cyber threats. non-genetic cardiovascular THE MYSTERIES OF THE MCBOATFACE
the first-row transition metals. disorders. EARTH’S BIGGEST NATURAL Professor Mike Meredith
CATASTROPHE Understanding how oceans
Professor Shanaka de Silva store carbon and heat to slow
Revealing the secrets of down climate change.
‘supervolcanoes’ and
supereruptions. 82 UNRAVELLING THE
SIGNALLING CUES

I do not think that people realise 66 ONE OCEAN, MANY MINDS:


COLLABORATIVE SCIENCE IN
CONTROLLING VERTEBRATE
REPRODUCTIVE BEHAVIOUR

how much science, especially


THE ARCTIC Dr Karen Maruska
DProfessor Igor Polyakov Investigating how animals

chemistry, impacts their lives.


Monitoring climatic changes in process and translate
the Arctic Ocean. multisensory social cues into
context-specific behaviours.

10
DR DONNA NELSON
Page 10
RESEARCH AREAS

Physical Sciences Health & Medicine Earth & Environment Biology

4 www.researchoutreach.org www.researchoutreach.org 5
Physical Sciences ︱ Dr Srikanth Patala

Understanding
why materials fail
S
After receiving a Young Investigator Program award ociety’s reliance on the properties of key components
from the US Air Force Office of Scientific Research, in critical structures – made up of metal alloys and ceramic
Dr Srikanth Patala and his research team at North materials – is without question. Of course, many of these
Carolina State University have studied the impact of materials perform well but require scheduled maintenance
‘grain boundaries’ on the structural integrity of many to detect defects, such as cracks or heat damage, before they
materials used in critical applications. This includes become serious or create a situation where a failure would blades rely on a polycrystalline Nickel Above: The polyhedral unit model of the Σ3(1 0 1̄) asymmetric tilt grain boundary is illustrated.
materials commonly found in jet engine turbine blades, threaten life. alloy. Cracks in these components can (a, b) The atomistic structure and the polyhedral units, along two different views (the tilt axis and
the plane normal), are shown. The polyhedral units corresponding to the smallest asymmetric unit
nuclear power stations and internal combustion engines. form at high temperature but their rate (the unit-cell) are highlighted. (c) The unit-cell polyhedral units, along with the overlapping voids
Materials used are often polycrystalline, meaning they of formation remains unclear. Evidence and the clusters of atoms that correspond to the polyhedral units, are shown. (d) The unique GB
comprise a structure made up of joining many regularly shaped suggests that the interfaces between units are the 9-atom unit and the 5-atom dual-tetrahedron. The dual-tetrahedron is split further
into two seed tetrahedra. The 9-atom GB unit best fits a 9-atom seed cluster in the data-base
crystals. For example, metals used in aircraft engine turbine crystals of the material – the grain with RMSD error of ~ 0.38. The error is calculated using the point-pattern matching algorithm.
boundaries – influence how materials
will fail. This area has been the subject
of Dr Srikanth Patala’s research.
Metals used in aircraft engine turbine
blades rely on a polycrystalline Nickel
CRYSTALLOGRAPHIES
Dr Patala and his team investigated alloy. Cracks in these components can
how crystals come together to form
a material and how its structure
form at high temperature but their rate
influences properties like rate of of formation remains unclear
diffusion, corrosion resistance,
conductivity, inter-granular cracking, atomistic structure of grain boundaries at grain boundaries has been made
resistance to failure and the impact represents a significant challenge but with an algorithm recently developed
of extreme environments. The one that would, if achieved, show how by Dr Patala’s team. The algorithm
geometry, or crystallography, of the influence of a collection of grain describes the structure as a packing
the interfaces between the crystals boundaries would affect the properties of three-dimensional polyhedra (a many-
is complex – it must describe three of a material. sided three-dimensional shape with flat
parameters called misorientation and sides – a cube is a polyhedron but they
two additional parameters for the This was the challenge that Dr Patala can have many more sides).
orientation of interface. This makes set himself and his team: to create a
a total of five dimensions to define reduced-order mathematical model that The creation of arrangements of 3D
the structure of each grain boundary predicted how polycrystalline materials polyhedra to model grain boundaries
rigorously. Dr Patala’s team developed would perform and discover how grain from a disordered set of atoms that form
tools to visualise the grain boundary boundaries would impact their ultimate a material is complex. Dr Patala chose
misorientations and to represent the strength, toughness and performance. to use the mathematical properties
variations of the properties of interfaces To overcome the complexity of grain of the well-established Voronoi network,
as the geometrical parameters are boundary structures, Dr Patala’s team a method of partitioning space, to
varied in the five-dimensional space. plans to adopt machine-learning automatically identify the network
algorithms that make use of pre-existing of three-dimensional polyhedra (whose
UNDERSTANDING STRUCTURE– and large databases of grain boundary vertices or corners represent the
PROPERTY RELATIONSHIPS structure–property relationships. atoms) that are present in the structure
In materials science, to predict of a grain boundary.
how a material behaves requires an MODELLING USING THREE-
understanding of the underlying DIMENSIONAL GEOMETRY Dr Patala’s team also developed
structure – i.e., how atoms pack together An important step in quantifying a pattern-matching technique that
to form the material. Computing the and understanding how atoms pack allows the comparison of the polyhedra

6 www.researchoutreach.org www.researchoutreach.org 7
Dr Patala and his team were then
Behind the Bench
Dr Srikanth Patala
found in the grain boundaries to a
pre-existing database of hard-sphere
packings (the way that atoms arrange able to analyse the voids in the grain
boundaries using the three-dimensional
themselves in a model material system).
This allows for the classification of E: spatala@ncsu.edu T: +1 919 515 3039 W: http://research.mse.ncsu.edu/patala/
the type of polyhedra observed in
grain boundaries and comparison polyhedral geometries
of their structure. Research Objectives Collaborators and Engineering. He was also given awards
interpose themselves within the grain classifying grain boundary structures. Dr Patala’s research interests include the • Christopher A. Schuh, Danae and Vasilis for an Outstanding PhD Thesis Research
While Dr Patala’s research has focused boundary, influencing the ultimate It will be possible to use the results structure of materials and the analysis Salapatas Professor of Metallurgy, by MIT and the James Clerk Maxwell Young
on the analysis of grain boundaries strength and toughness of structural in autonomous learning algorithms to of defects, particularly focusing on their Massachusetts Institute of Technology, Writers Prize by the Philosophical Magazine
in aluminium, his findings are applicable materials (e.g., through hydrogen discover a fundamental set of polyhedral interactions in polycrystalline materials, USA. & Letter, both in the same year.
and in design principles that improve the • Eric R. Homer, Assistant Professor,
to most metals, ionic solids and embrittlement). units at grain boundaries, improving
performance of structural and functional Mechanical Engineering, Brigham Young Contact
some ceramics. However, they are understanding and allowing prediction
materials. University, Utah, USA. Dr Srikanth Patala
not applicable to organic materials, WHY THE RESEARCH MATTERS of properties – such as resistance • Arash D. Banadaki, Postdoctoral Materials Science & Engineering
which have directional bonds that Dr Patala’s research has shown that it to failure. Funding Researcher, Materials Science and North Carolina State University
define their material structure. This is is possible to generate a coarse-grained • National Science Foundation USA (NSF Engineering, North Carolina State 3028C Engineering Building I
a focus of future research in Dr Patala’s geometric description of the structure Void structures can also be classified USA), Faculty Early Career Development University, North Carolina, USA. 911 Partners Way, Campus Box 7907
research group. at grain boundaries, and especially using Dr Patala’s research outcomes Program, DMR #1554270 Raleigh, NC 27695-7907
• AFOSR Young Investigator Program, Bio USA
the atomic packing. They expect their and it is anticipated that this information
Aerospace Materials for Extreme Dr Patala was awarded his PhD by
VOIDS MATTER model to replace the traditional will be utilised to identify potential Environments, Contract #FA9550-17- Massachusetts Institute of Technology (MIT)
Using the polyhedral geometries allows structural unit model currently in use. segregation sites where there are 1-0145 in 2011 where he studied Materials Science
for the identification of voids – the Grain boundaries that are similar in solute atoms at grain boundaries.
space that is unoccupied by atoms – terms of their crystallography can now The developed mathematical model

Q&A
in the grain boundary region. Evidence be compared. highlights a link between analysed
suggests that the structure of voids, or grain boundary structures and those structure to properties (such as diffusion, the performance of materials under
the free-volume, at grain boundaries The rigorous mathematical approach observed in metallic glasses, paving corrosion resistance, conductivity, etc.) extremely high temperatures. In these
of interfaces. To accomplish this, we are environments, it is the grain boundaries
influences material properties. This is and comparison of the results obtained a way to evaluate grain boundaries
Your research focuses on the structure building a database of properties using that tend to fail first. Therefore,
similar to observations in amorphous with a database of rigid hard-sphere using the theories proposed of aluminium and you suggest that high-throughput simulations of interfacial developing quantitative structure–
or metallic glass metals – those with packings provided a robust basis for for amorphous materials. it is applicable to other metals, ionic phenomena. By using the structural property relationships of interfaces
a more disorganised structure at the solids and some ceramics. Can you features of the grain boundaries and the will not only help us understand how
atomic scale. Grain boundaries are explain why this is so and expand data generated, robust structure–property materials fail but will also help design
disordered and Dr Patala anticipated on the types of ceramics where relationships can be constructed using materials that can withstand extreme
that modelling a polyhedral unit your research is applicable? machine learning algorithms. environments that are of interest to the
The current limitation of the technique US Air Force.
structure that analysed the void content
Below: The polyhedral unit model of the Σ11(1 1̄ 3) grain boundary is illustrated. (a, b) arises from the nature of the bonding The mathematics of your model is
of a material at grain boundaries would The atomistic structure and the polyhedral units (capped trigonal prisms (CTP)) of the symmetric- in materials. Primarily, bonding can be complex, mirroring the complexity of It seems that you have improved
prove beneficial, offering practical tilt boundary, along two different views (the tilt axis and the plane normal), are shown. The CTP metallic (found in metals), ionic (found grain boundary types. Can you explain science’s understanding of grain
applications. For example, identifying corresponding to the smallest asymmetric unit (the unit-cell) is highlighted. (c) The CTP and in most ceramics) or covalent (in covalent why you selected Voronoi network and boundaries in materials. How do
the overlapping voids, along with the clusters of atoms that correspond to the CTP, are shown.
the voids in the grain boundary would Also illustrated is a comparison between the observed and a perfect CTP unit obtained using ceramics and polymers). Metallic and Delaunay triangulation, and whether you see the research progressing
help understand how small solute atoms a point-pattern matching algorithm. ionic bonds are non-directional, i.e. the any other approach was considered? from here?
energy does not depend on the direction I would actually say that the technique As I had mentioned earlier, computing
or the orientation of the bond. In covalent of using Voronoi network for identifying the structure is simply the first step in
solids, the bond energy depends polyhedral units is pretty simple. Voronoi understanding material properties.
on the angles between the bonds analysis is a technique taught in most We are developing novel ways to
(directionality) and hence the geometries undergraduate mathematics classes. describe this structure that can be used
are constrained. Therefore, a polyhedral We use the property of Voronoi networks as input to machine learning algorithms.
model might not work very well for to identify which atoms should be joined These algorithms will then be combined
covalent solids (like carbon, silicon etc.). together to form the polyhedral units. with high-throughput simulations and
We are currently developing tools for The simplicity of the technique is also experimental measurements to develop
describing such structures. what makes it powerful and applicable to the relationships between the structure
many different grain boundary types and of grain boundaries and their properties.
You mention machine learning as a material systems.
potential next stage for your research.
Could you elaborate on this? How do you see the results of your
Representing the grain boundary work assisting your main sponsor,
structure as a combination of polyhedra is the US Air Force?
one step in understanding the properties The Air Force Office of Scientific
of materials. The next step is to relate the Research is interested in understanding

8 www.researchoutreach.org www.researchoutreach.org 9
Thought Leader

ACS: Taking
chemistry to
Hollywood
Science is everywhere. From your sofa to your car, pretty much any product
you can think of would not exist without the work of science, and chemistry in
particular. This fact is often under-appreciated by the public, but for Dr Donna
Nelson of the American Chemical Society, she has made it her mission to
change this. Following her work as the science advisor to Breaking Bad, she now
hopes to continue her Hollywood adventure in the hope of changing the public
perception and appreciation of science. We at Research Outreach recently spoke
to her about this and much more.

B
reaking Bad is regarded by many our collective role is to represent the ACS
as one of the best American TV to the public. It is a voluntary position,
drama series ever. The numerous so the members very much want to
awards it has picked up over the years hear from us, because we represent
are testament to this. For those who them. Within that, each president gets
have not seen it, the show centres on a to choose their own projects, related to
school chemistry teacher who turns to something they are particularly interested
drug manufacture in order to fund his own in, or knowledgeable about. For me, I am
cancer treatment. very interested in communicating science
to the public, which is also one of the
The science underpinning each episode, reasons why I became the science adviser
especially related to the process to Breaking Bad.
behind the production of crystal meth,
is fundamental to the show’s success. What impact do you think Breaking
And it is here that Dr Donna Nelson’s Bad has had on the public, with
work as the show’s scientific advisor regards to chemistry?
has proved pivotal. I think it has moved everybody’s
knowledge of chemistry forward. I
Away from her Hollywood duties, have given hundreds of talks about the
Dr Nelson is also the Immediate Past show, and at the end there is a Q&A Bad is what inspired them to start these
President of the American Chemical
Society. She recently sat down with
period. Each time there are people in
the audience who know more about
blogs in the first place, so I am absolutely
positive that it has influenced a great I do not think that people realise how much science,
us at Research Outreach to discuss her
role further, outlining why changing the
Breaking Bad than I do, because they
became so enthralled with it. One of
number of young people.
especially chemistry, impacts their lives
public perception and appreciation of the things that really amazed me about I think a lot of people may not have
science is so important. it was the number of students who known about the Drug Enforcement
would tell me they had become much Agency (DEA) beforehand either. For Why is it important to you to improve perception of science. People watch TV and Engineering News – the American
Hello Donna! What does your role more interested in science because of instance, the show had assistance from the presentation of science to the series every week from their own living Chemical Society’s weekly magazine.
as Immediate Past President of it. Some even phoned me up wanting the DEA on what the equipment in illicit public, and ensure its accuracy on TV? rooms, so I decided it was Hollywood He was saying that neither he, nor any
the American Chemical Society quotations for their own science blogs, meth labs should look like. They also The main reason is to influence the public that we needed to reach out to – but at of his writers, had any formal science
(ACS) involve? which of course I am always happy to advised which steps to omit from being to appreciate science. I found that it was the time it seemed impossible. That was background or education. They were
There are three of us in presidential provide. It is amazing how many times shown on TV – they did not want it to be Hollywood, the television and the movies, until I read an article written about the having to research their science content
succession simultaneously, and part of young people have said that Breaking a cookbook for making illicit drugs. that had a real impact on the public’s show’s creator, Vince Gilligan, in Chemical through the web. It was really important

10 www.researchoutreach.org www.researchoutreach.org 11
Thought Leader

The American Chemical


to Vince to get the science right, and related information and knowledge- good job now of increasing the education Society Building, in
Washington DC
it was proving to be really difficult. I based solutions. A good example of aspect of science – there is a lot of science
read that and decided to volunteer this is the Chemical Abstracts Service built into TV shows and even in our
my expertise. (CAS), which assigns CAS numbers schools, etc. – but I do not think there is
to chemical substances. The service is a necessarily an appreciation for science.
Breaking Bad was good because it helped division of the ACS, and was developed The general public are certainly becoming
to get science out there, but we still have to overcome the limitations of other more science literate, and the students
a long way to go. It definitely benefitted chemical naming systems. that come into my class now are so much
me though, because it gave me a peek smarter than they were 20 years ago, but I
into how Hollywood operates. This is important for everybody who do not think that people realise how much
manufactures almost anything, because science, especially chemistry, impacts
What was your input to the show? of the CAS number that is used to their lives. You cannot name anything
I gave input when they contacted me identify each chemical. Even attorneys that does not contain chemicals, except
saying they were putting something into and business people know that the CAS a vacuum. Every single thing – car parts,
the script involving science. They would number is used to identify chemicals, furniture, carpeting, clothing – contains

I am very interested in communicating science to the public,


which is also one of the reasons why I became the science
adviser to Breaking Bad

send me pages out of the script, asking but they may not know that the number chemicals and people do not really fully
me to draw chemical structures that they actually comes from the ACS. appreciate that. That is why we have
would put on the blackboard, or help that as one of the ACS’ goals – to make
them with the pronunciation of certain The second part is about helping the public not just understand science,
words or dialogue. I made set visits members advance their careers. but genuinely appreciate it.
and was able to actually meet the actors I am particularly happy with the way that To combat these, at the next ACS society for the US. So, that is where the
and answer their questions about how the ACS gives under-represented groups What impact do you think the ACS National Meeting we are going to have a ACS was actually born – at that meeting
scientists talk to each other, how they talk opportunities that one might not be able has had on advancing the broader symposium on how chemistry and science and at that house.
to their students, and what type of person to get in academia or in the industry chemistry enterprise since it was are presented in Hollywood, on TV and
becomes a scientist. where they work, enabling them to get first established 140 years ago, in the movies. For the jobs issue, we From a more personal perspective,
training and learn about leadership. and are there any accomplishments created a task force of people to look into your research into organic chemistry
Can you tell us more about the ACS’s you are particularly proud of? it. I am currently in the process of writing and long-term commitment to
background and what the aims The third part relates to education. ACS I think the ACS has had a huge impact up the results. chemical research has seen you win
of the society are? have their own self-certified degree, which on every single scientific development, numerous awards over the years. What
The ACS has a four-part strategic plan. students only receive if they take certain but particularly in two broad categories Under the National Historic Chemical does winning these awards mean
The first part relates to its publication unit, courses and fulfil certain requirements. – the Chemical Abstracts Service and Landmarks program, the ACS to you? ACS President Donna Nelson
which provides the very best chemistry- SciFinder. SciFinder, also produced by grants landmark status to seminal It means a great deal. One of the
The fourth goal is CAS, is a comprehensive database of achievements in the history of the awards which I won early on was a
to communicate chemical literature and is a core research chemical sciences and provides Guggenheim Award, which is very
chemistry’s value tool. A lot of chemists do not understand a record of their contributions to prestigious. I am very proud of that and
to the public and what has gone into that, but it has been chemistry and society in the US. I think that these things help you in your
to policy makers, an immense effort. For you, which landmark has had career. I remember when I was nominated
including members the greatest impact? for ACS Fellow I kept telling myself it
of Congress. This What developmental goals have you I really enjoyed visiting the birthplace was okay if I did not win, because I did
is very important to chosen for the ACS while you serve of the American Chemical Society in not want to be disappointed. But then
American Chemical Society
me, because when I as the society’s primary spokesperson Pennsylvania. It all began in a house when I was elected to ACS Fellow, it 1155 Sixteenth Street, NW
speak to people I will and representative? that once belonged to Joseph Priestley, meant everything. I think awards generally Washington, DC 20036
often say that I do When I ran, I told the membership that who discovered oxygen in 1774. It is still are very important – they certainly help USA
not think the public I would try to accomplish whatever goals there and it has been converted into a one’s career, as they give you credibility
appreciates scientists they wanted. I also sent emails out to museum. Amazingly, his lab is still there in your work. E: service@acs.org
or science enough. every single member asking them what as well. On the hundredth anniversary of
W: http://www.acs.org
Most science concerns they had. There were two main the discovery of oxygen, a lot of chemists
organisations and ones. One was about jobs and the other met at his house and it was through a @AmerChemSociety
Dr Donna Nelson with Bryan Cranston (left) and Aaron Paul, during the government was about the public perception of discussion at that anniversary celebration /AmericanChemicalSociety
a Breaking Bad set visit. have done a pretty science – which is my area of interest. that they decided they needed a chemical

12 www.researchoutreach.org www.researchoutreach.org 13
Physical Sciences ︱ Prof Roy L. Johnston and Dr Francesca Baletto

Designing catalysts bit by bit


Catalysis, using reagents catalytic species that are efficient, means that the computational models
to speed up chemical robust and cost-effective. However, need to trial a huge number of different
reactions, is big business. intelligently designing new catalysts configurations and particle sizes to
From synthesising new chemicals or predicting which materials are likely explore which combination of structural
to cleaning up the exhaust to be successful in the lab relies on a features will give rise to the most
fumes from cars and sustainable deep understanding of the intricacies promising catalysts.
energy devices such as hydrogen of catalytic mechanisms, another very
fuel cells, catalysts play a huge challenging problem in itself. Prof Roy Despite the challenges in constructing
role in our daily lives. Prof Roy L. Johnston and Dr Francesca Baletto accurate models, the advantage of the
L. Johnston and Dr Francesca at the University of Birmingham and methods used by Prof Johnston and Dr
Baletto at the University of King’s College London, with their Baletto is that the calculations provide
Birmingham and King’s College collaborators, are developing and a level of detail about the catalytic
London respectively are using applying computational techniques for mechanism that it is simply not possible
novel computational approaches exactly this problem, via the design and to capture in laboratory experiments.
not just to understand the tailoring of nanomaterials for catalysis. For example, it was experimentally
intricate mechanisms of how
known that the introduction of
such catalysts work but to use
CATALYSIS BIT BY BIT additional strain in the layers of atoms
this knowledge to design new,
Modelling catalytic materials at the surface of the catalysts could
more efficient nanocatalysts
computationally is no mean feat. result in different chemical properties
for particular applications.
While computational modelling can to those of the unstrained surface
be used to predict the outcomes of of the same elements. However,

C
simple gas phase chemical reactions the mechanism underpinning this
atalysts speed up chemical very accurately, modelling solids, and observation was not understood until
reactions by lowering the energy particularly those with heavy atoms like the corresponding computational
required for the reaction to occur. metals, offers a number of additional modelling was performed.
To achieve this, the catalyst forms an challenges. Prof Johnston and Dr
intermediate complex with the chemical Baletto are also particularly interested Even greater levels of complexity
reactants, to provide a lower energy in the properties of more unusual are introduced into the computational
route to reaction. These intermediate materials, known as nanoalloys, which models by potential transformations
complexes are typically short-lived as, have numerous desirable and enhanced of the structure of the catalyst
to allow the catalytic cycle to continue, catalytic properties. These nanoalloys during a reaction event. While such
the catalyst needs to be ‘refreshed’ are nanoparticles which are made up changes in the shape of the catalyst
so it can be used in future reactions. of two or more metallic elements. may be rare events, it is necessary
to account for these possibilities in the
There are many types of catalysts Computational modelling of a catalytic computational modelling to accurately
made up of a whole variety of different reaction requires an understanding of reproduce experiments. As well as the
chemical elements. Some of the most

Johnston and Baletto aim to tune


commonly used elements are transition
metals because they can interact with
a wide variety of chemical species.
These elements can also be arranged
catalysis at the nanoscale using state-
in a variety of ways to make catalysts of-the-art numerical and computational
with different shapes and structures,
that can have a dramatic effect on their techniques
efficiency and properties.
the structure of the catalyst itself as well development of new catalytic materials,
As catalysts play a key role in processes as any substrates it interacts with. The this is also driving the development
such as the removal of toxic carbon nanoalloys that Prof Johnston and Dr of new computational methods, as
monoxide from exhaust fumes, Baletto study are particularly complex part of the TOUCAN project (‘Towards
there is a huge need to develop new as they come in a variety of sizes. This an Understanding of Catalysis on

14 www.researchoutreach.org www.researchoutreach.org 15
Behind the Bench
Professor Roy Dr Francesca
Johnston Baletto
E: r.l.johnston@bham.ac.uk T: +44 121 414 7477 E: francesca.baletto@kcl.ac.uk T: +44 2078482152

Research Objectives Prof Johnston and He has published approximately 250 journal More info:
Dr Baletto use computational techniques articles, reviews, books and book chapters. • toucan.bham.ac.uk
to design and tailor nanomaterials, focusing • www.chem-res.bham.ac.uk/johnston
on nanoalloys and their catalytic properties. Francesca Baletto is a Senior Lecturer in Physics • http://bit.ly/2wgY9f5
at King’s College London, UK. She is authors • www.balettogroup.weebly.com
Funding of more than 45 journal articles, reviews, and • www-wales.ch.cam.ac.uk/CCD.html
EPSRC (Critical Mass Grant EP/J010804/1 and EP/ book chapters. www.ucl.ac.uk/klmc/Hive/
J010812/1)
Contact
Collaborators Professor Roy Johnston External Collaborators:
Other PIs on the TOUCAN Project: School of Chemistry Professor Dr Rolf Schaefer (Technical University
Prof Gábor Csányi, Prof Chris Pickard, Prof David University of Birmingham Darmstadt, Germany); Prof Micha Polak (Ben
Wales (University of Cambridge); Dr Jonathan Edgbaston,Birmingham Gurion University of the Negev, Beer Sheba,
Doye (University of Oxford) B15 2TT, UK Israel); Prof Marcela Beltran (UNAM, Mexico);
For external collaborators visit: Dr Laurent Piccolo (CNRS, Lyon, France); Prof
toucan.bham.ac.uk Dr Francesca Baletto Roberto D’Agosta (ETSF-Nanobio, EHU/UPV,
Physics Department San Sebastian, Spain); Dr Caetano Miranda
Bio King’s College London (USP, Sao Paolo, Brazil); Dr L. Oliver Paz-Borbon
Roy Johnston is Professor of Computational WC2R 2LS, UK (UNAM, Mexico)
Nanoalloys’), a collaborative network Rational design of nanocatalysts implies finding the best shape for a target reaction. Sampling the Chemistry at the University of Birmingham, UK.
energy landscape of nanoparticles in the gas phase (A) and supported nanoparticles (B) and extracting
of projects focused on understanding
possible structures; (C) calculating the binding energies of a reagent onto the nanoparticles. Here

Q&A
how nanoparticles and nanoalloys can we illustrate the adsorption of O2 onto Pt clusters of ~55 atoms, displaying a cuboctahedral (CO) or
speed up chemical reactions. decahedral (Dh) shape, which have been deposited onto pristine MgO. Atom colour code: Red refers to the manufacture of highly efficient catalysts, needed to shape nanocatalysts with the
oxygen, blue to platinum and green to Mg. controllable at the molecular scale, becomes most promising characteristics, based
feasible at a reasonable cost. The combination on the use of descriptors which will define
GREENER ENERGY
What do you think are some of the biggest of numerical and experimental tools is mandatory proper design rules.
One of the key reasons that Prof unsolved problems in catalysis today? to achieve the required control. • As density functional theory is at the core

Johnston and Baletto are searching


Johnston and Dr Baletto are so • Developing cheaper catalysts, by replacing of catalysis modelling, the choice of pseudo-
interested in nanoalloys over traditional, or reducing scarce metals such as Pt and What do you think are some of the most potentials with the right level of accuracy
exciting developments in catalysis that have
for descriptors to relate the structures
other precious metals. is important, with an eye to size scalability.
substrate-supported monometallic • Knowledge of the atomistic mechanisms, arisen from using computational modelling in • A dynamical model for understanding
catalysts is the potential impact they including reaction kinetics and intermediate this area? chemical reactions in a realistic environment,
could have in the field of sustainable of metallic nanoparticles to their formation and the effect of the surrounding
environment. This will allow the correlation
The most exciting idea is the growing idea
that chemistry can be tuned by modifying
including atomic mobility within each
nanoparticle.
energy and clean technology. They
have studied the impact of nanoalloys catalytic performance of nanoshapes with catalytic properties,
leading to new design rules.
nanoparticle shape, leading to a completely
new approach to catalysis which is only feasible
• New numerical tools are needed to
understand the assembly of nanoparticles
in the catalysis of a variety of reactions, • Modelling nanocatalysis as a dynamic at the nanoscale. In this regard, a hot topic is into super-architectures and the influence this
including the oxygen reduction process occurring at high temperatures the search for descriptors, which are measurable can have on catalysis.
and pressures, in the presence of various quantities that link nanoparticle shape and
reaction (ORR), which is of importance platinum by replacing some of the computational approaches, that can
reactants and products. This will be chemical composition to their catalytic activity Do you think it will be possible to deduce
in electrochemical fuel cells, and the platinum content with a cheaper metal. be used to predict the properties facilitated by the development of new and selectivity. Finding robust descriptors will general intuitive chemical models for
oxidation of carbon monoxide (CO). Prof Johnston and Dr Baletto have been of a variety of catalytic species. All theoretical methods which are able to open the possibility of developing a dynamical catalyst design from your work?
As well as being a toxic pollutant, CO modelling the effects of the amount of this is helping to drive ‘intelligent’ capture and analyse various elementary model for nanocatalysis, where the substrate Yes, the search for and definition of
steps including the structural, and hence is also mobile. Numerical tools have begun to geometrical descriptors in conjunction
is one of the main poisons of fuel cell of substitution in the nanoalloys, for catalyst design. This will help identify electronic, evolution of the nanosystems. be used to elucidate the role of the surrounding with experimental data – e.g., electron
catalysts; it decreases the efficiency a range of different metals, to see if and pre-screen species that are likely environment, at least as far as it stabilises microscopy – will open a new way to design
of the platinum electrodes, which are they can identify which metals, and to be successful candidates, essential Do you think nanocatalysts will be the particular shapes and chemical ordering nanocatalysts in an intuitive fashion. The use
dominant type of catalyst in the future? of nanoparticles of machine learning is also likely to shed new
incredibly costly to replace due to the how much of each one, are required not just as a cost-saving exercise
Yes, since nanoparticles allow the tailoring insights on how catalytic activity depends
increasing scarcity of platinum. to design novel, highly efficient but to accelerate the development of catalytic properties by changing the What are the main challenges to be on nanoparticle shape, size and chemical
and selective catalysts for reactions of a new generation of catalysts in elemental composition and ordering, shape overcome for computational methods ordering, leading to new and fascinating routes
Unfortunately, there are many existing such as CO2 capture and reduction, clean technologies. and morphology, which in turn tunes the to achieve ‘chemical accuracy’ in describing for nanocatalyst design. Existing optimisation
electronic properties of the nanoparticle. The catalytic processes? tools can be adapted to explore the pool
catalysts for which platinum is an and O2 reduction. global market for nanocatalysts is continually • To include all aspects of the environment of the of candidates which maximise/minimise the
essential component and it has been expanding and this trend is forecast to catalyst, including the support (usually a metal geometrical quantities of interest, eventually
challenging to find chemical elements The work of Prof Johnston and continue for the near and medium-term future. oxide material), temperature, pressure, solvent providing guidelines for the synthesis of
Metallic, multimetallic (mixing precious and (for solution phase catalysis) and any surface- these nanoparticles.
that can act as a suitable replacement. Dr Baletto is helping to provide an
abundant metals) and hybrid (e.g., metal-metal bound but non-reactive ligand species.
However, platinum nanoalloys offer unparalleled insight into exactly how oxide and metal-biomolecule) nanoparticles • Atomistic methods in combination with machine
a route to making catalysts that are catalysts work, as well as leading will play an increasingly important role, once learning tools can achieve the desired accuracy
as efficient, but require much less the development of new, general

16 www.researchoutreach.org www.researchoutreach.org 17
Physical Sciences ︱ Professor Mark Keane
Coupled dehydrogenation (of Reactant 1) to give Product 1 with hydrogenation of Reactant 2 to Product 2

Cleaner pathways
to chemical synthesis via
new generation catalysts
M The majority of hydrogen is produced
The synthesis and manufacture any modern materials and and there are environmental penalties Perhaps one of the most surprising
of chemicals, and chemical chemicals start their lives as associated with their extraction and compounds to be sourced from fossil
products, has typically relied fossil fuels. From plastics to processing. Potentially increasing fuels is hydrogen. The majority of from natural gas in a process requiring
on petroleum-based feedstocks. petrol, fossil fuels, such as crude oil and fuel prices may make it prohibitively hydrogen is produced from natural
Even hydrogen, often hailed natural gas, are still widely used for the expensive to extract the chemical gas in a process requiring very high very high temperatures that also
produces carbon dioxide
as a ‘clean fuel’ and an important extraction and synthesis of many of the species that are the essential starting temperatures that also produces
component in many chemical chemical compounds we rely on in our ingredients for many synthetic carbon dioxide. Despite the seeming
reactions, is sourced from such daily lives. The problems with this are procedures, such as the manufacture abundance of hydrogen atoms as part
feedstocks. However, Professor obvious. Fossil fuels are finite resources of drugs or polymer materials. of water molecules and hydrocarbons, facilitated by the presence of a catalyst. University has been finding ways to
Mark Keane’s research at Heriot- molecular hydrogen (H2) is actually very These reactions are ubiquitous in modify the catalysts for hydrogenation
Watt University is developing rare on Earth as the majority escapes industrial synthesis; they are how reactions. This is to both reduce,
methods for clean chemical from the atmosphere. vegetable oils are processed into fats, or eliminate, the need for hydrogen
production from alternative, such as margarines, or to make paraffins in these reactions, finding new ways
renewable feedstocks. To However, hydrogen is a key component and naphthenes for use as fuels. of exploiting alternative sources
achieve this, he is designing
in one of the most important types of hydrogen that have a much lower
and developing new generation
of chemical reaction, hydrogenation. With few alternative methods for environmental impact.
catalysts that not only open
Hydrogenation reactions involve the hydrogen production that are not
up numerous possibilities in
addition of molecular hydrogen to reliant on the use of fossil fuels, BIOMASS FEEDSTOCKS
chemical synthesis but also use
alternative sources of hydrogen another compound and are usually Professor Mark Keane at Heriot-Watt One reaction that Prof Keane has
for such reactions. been particularly interested in is the
transformation of furfural to furfuryl
alcohol. Furfural is a molecule derived
from biomass, such as corncob and
sugar cane, that can be selectively
hydrogenated to form highly valuable
furfural alcohol used in manufacturing
resins, rubbers, adhesives and as
a building block for drug synthesis.
There are also many chemical
derivatives that have numerous
applications in polymer synthesis.

The ability to obtain such building block


chemicals from non-petroleum sources
is of pressing urgency but one of the
problems with furfural hydrogenation
and processing has been the use of
very environmentally damaging copper
chromite catalysts. Prof Keane has
developed an alternative approach for
this reaction, making use of a specially
designed catalyst that does not just
2-butanol dehydrogenation to 2-buanone over nano-scale supported Cu with hydrogen release pose less environmental risk but
and use in the selective hydrogenation of furfural to furfuryl alcohol over nano-scale supported Au reduces hydrogen usage in the process.

18 www.researchoutreach.org www.researchoutreach.org 19
OGENATIO
N Behind the Bench
HYDR Professor Mark Keane
E: m.a.keane@hw.ac.uk T: +44 (0)131 451 4719
W: https://www.hw.ac.uk/staff/uk/eps/mak.htm

Furfuryl alcohol
O H
O
FOOD CROP WOOD Research Objectives Bio Contact
RESIDUES WASTES Professor Keane’s work is directed at clean Mark A. Keane is Professor of Chemical Prof Mark A Keane
chemical production using bio-derived Engineering at Heriot-Watt University. He Room NM2
O Biomass derived compounds feedstock with a particular focus on was Professor of Chemical & Materials John Coulson Building

VALORISATION
O
H alternative sources of hydrogen for reaction. Engineering at the University of Kåentucky Heriot-Watt University
HYDROGEN-
Au INPUT
and Senior Lecturer at the University of Edinburgh
Furfural H Funding Leeds. Author of over 190 publications, Scotland

COUPLING
FREE SELECTIVE
H2

EPSRC his research deals with the synthesis/ EH14 4AS


HYDROGENATION H characterisation of new generation catalysts UK
An ideal catalyst is one with application in cleaner processing and
that selectively promotes environmental catalysis.
formation of the desired O Cu OUTPUT
reaction product, does so

Q&A
with good efficiency and High value chemicals products are readily separated by to establish the range of applicable
has the longest possible 2-Butanone standard distillation. This is an example reactants. Any increase in oil prices will
lifetime before degradation
O H of advanced process intensification drive the demand for biomass-derived
of the catalytic material occurs. How easy are these coupled catalysts directed at enhanced energy efficiency platform chemicals. One potential
For furfural hydrogenation, to synthesise? and is applicable to a range of industrially bottleneck is the cost of effective chemical
The catalysts for reaction coupling relevant dehydrogenation/hydrogenation extraction from biomass, which is being
H
gold-based catalysts have been
D

2-Butanol DRUG

YD
SYNTHESIS contain a dehydrogenation (e.g., Cu) combinations. addressed in biorefineries. Drawing on
E

used with some success as they have


and a hydrogenation (e.g., Au) metal technology used in the pulping industry,
very high selectivity for the desired
RO POLYMER RESINS SOLVENTS component on an oxide carrier or support. Can you easily predict which metals are furfural can now be produced from
hydrogenation product.
GE Catalyst preparation involves standard likely to be good candidates for such a variety of cellulosic feedstocks.
NA coupled catalysts?
TIO N
chemical impregnation or precipitation
The major drawback with gold catalysts techniques that are widely employed Gold is inactive in dehydrogenation but Do you think it will be possible to
has been the relatively slow reaction in a range of applications. Metal loading highly selective in hydrogenation. Copper make very general coupled catalysts
rates, so commercial use of such is controlled by varying metal precursor shows high dehydrogenation activity. for a wide variety of chemical
concentration and pH. Metal particle In designing coupling catalysts, the first reactions?
catalysts also involves using an excess Use of biomass feedstock in coupled dehydrogenation/hydrogenation for the production of an array
of high value products size and surface composition are tuned approach is to keep both metals segregated It is striking that the number of published
of pressurised hydrogen to compensate
by altering activation temperature. on the oxide carrier with effective transfer studies on coupled heterogeneous
for this. The use of highly pressurised Support  acid-base and redox properties of reactive hydrogen from copper to gold catalytic dehydrogenation/hydrogenation
gases comes with many safety concerns are important surface characteristics that sites where hydrogenation proceeds. There systems is still so limited. This may be
and a large proportion of the hydrogen can determine overall performance. are other transition metal combinations due to the requirement for a catalyst
used in this way is essentially wasted to produce the hydrogen required of formic acid, a side product of many where this can apply but this requires that is active for both dehydrogenation
as it remains unreacted. Prof Keane to fuel the reactions at the gold sites. biorefinery processes, as a source of Do you think this approach will parallel testing to ensure conditions where and hydrogenation. Differences in
be applicable to all industrial the rate of dehydrogenation (hydrogen reactivity of the two reactants, the
has been designing so-called ‘coupled All that is required is a chemical that hydrogen for such reactions.
hydrogenation and dehydrogenation supply) matches hydrogen utilisation. possibility of cross-reaction between the
catalysts’ that use a combination can act as a suitable feedstock for the reactions? One interesting feature is the possibility of target products and/or reactants and
of metals, such as gold and copper complementary reaction. Prof Keane’s approach is easily Coupling endothermic dehydrogenation supported alloy formation at the nanoscale, ease of product separation are crucial
as a solution to this problem. These have scalable to large-scale, continuous with exothermic hydrogenation which may disrupt or enhance coupling. considerations. At this juncture, we are
increased hydrogen utilisation by several FUTURE OF INDUSTRIAL SYNTHESIS flow chemistry, which is a far more presents critical advantages in terms This is currently under investigation. some way from considering the possibility
orders of magnitude in comparison Already, Prof Keane and his group have efficient approach to chemical synthesis of thermal efficiency, lowering capital of a single catalyst for a variety of chemical
to the exclusively gold catalysts. been able to successfully extend this than the conventional production and operational costs. In addition to What are some of the remaining reactions/products. Work must first
circumventing use of external pressurised challenges for using biomass focus on bespoke catalysts for particular
approach to developing new generation of single batches. His future work
hydrogen gas, the hydrogen generated as a feedstock? reactant(s) combinations where catalyst
The reason these coupled catalysts catalysts for other important reactions to will continue to involve extensive from dehydrogenation is more reactive, Our results establish that reaction coupling selectivity is paramount.
are so efficient is because they combine generate amines and imines with myriad collaboration with industry, tackling leading to higher rates and increased harnessing hydrogen from dehydrogenation
complementary hydrogenation and uses in chemical synthesis. Such coupled chemical synthesis problems of global product throughput. Our work has results in greater hydrogenation rates
dehydrogenation reactions on the two reactions offer not just a safer route to importance with catalysts that offer focussed on a continuous coupling and full hydrogen utilisation for model
metals present. At the gold site, the large-scale chemical synthesis but also routes to far cleaner and greener of 2-butanol dehydrogenation (to reactants derived from biomass. Reaction
2-butanone) with furfural hydrogenation coupling is still at the developmental stage
normal hydrogenation reaction occurs, one that allows far more efficient use chemical synthesis and a reduction
(to furfuryl alcohol) where the two with fundamental kinetic data required
but at the copper site, a complementary of hydrogen. Recently, Prof Keane has of our reliance on petroleum feedstocks.
dehydrogenation reaction occurs also been able to demonstrate the use

20 www.researchoutreach.org www.researchoutreach.org 21
Physical Sciences ︱ Professor Anthony Serianni

Seeing the structures


of molecules:
There are still very few experimental
techniques capable of identifying
molecular structures, particularly
in the solution phase. X-ray
crystallography is probably the most
famous structural identification

insights from NMR and industry technique, with the 1964 and 1962
Nobel Prizes in Chemistry both being
awarded to work determining the

I
structure of biochemical substances
Many of the essential chemical constituents of life, dentifying the structure of molecules remains a key challenge including vitamin B12 and globular
including carbohydrates, are made up of complex within modern chemistry. In many cases, a  molecule’s structure proteins, respectively. However, X-ray
atomic arrangements. Knowing the particular structure has a huge influence on both its  chemical and biological crystallography relies on forming
of a compound is important not only for identification activities. For example, carvone, a molecule found in many a solid, crystalline sample, often
purposes, but also for understanding how biologically essential oils and fragrances, can either smell like caraway technically challenging and not always
relevant compounds react. Through this knowledge, seeds or spearmint, depending on the orientation of one of representative of the environment
their biological functions can ultimately be deciphered. the chemical substituents in the molecule. While the two forms in which a compound exists in vivo.
Professor Anthony Serianni at the University of of carvone are identical in their  atomic composition, it is the It was not until advancements in
Notre Dame has developed a wealth of experimental physical orientation of one of the groups in the molecule that nuclear magnetic resonance (NMR)
approaches to understand the 3D structures of such determines which receptors interact within the human nose and in the 1970s that it was possible to
systems, creating widely applicable techniques for ultimately, how we perceive the smell. capture information on the structure
structural identification. of molecules in solution. (A) Structure of a Man6 hexasaccharide containing eight sites of 13C enrichment (♦) chosen to optimise
the measurement of redundant J-couplings across its constituent O-glycosidic linkages. (B) Structure
of a mature high-mannose N-glycan, Man 9GlcNAc2, appended to protein. The subfragment
The underlying physics of nuclear highlighted in red corresponds to the structure in (A).
magnetic resonance (NMR)
spectroscopy is more widely
appreciated in the form of magnetic
resonance imaging (MRI), a technique
Professor Anthony Serianni at the
used in hospitals to image organs and University of Notre Dame is an expert
in utilising modern isotope-based NMR
diagnose diseases. In chemistry, rather
than identifying the type of tissue, NMR
can be used to identify the chemical
groups found in a molecule and their
techniques and computational approaches
relative connectivities. NMR signals can
be translated into chemical structures SWEET STRUCTURES into specific sites in the compounds.
for a wide variety of molecules, from Saccharides are a large family of An isotope is a version of a chemical
small molecules to large proteins, molecules, including sugars, starch element that has a different number
either as solids or liquids. and cellulose, made mostly from carbon, of neutrons that, in an NMR
oxygen and hydrogen. Saccharides experiment, acts as a unique flag for
Professor Anthony Serianni at the are also known as carbohydrates and the labelled element in the compound.
University of Notre Dame is an expert are ubiquitous in the biological world. This is very powerful when looking at
in utilising modern NMR techniques Understanding their chemical structures chemical reactions, as it is possible to
and computational approaches to is often key to understanding how they follow the position of the label during
identify the structures and reactivities will bind and interact with the receptors the reaction to identify the structures
of carbohydrates and nucleic acids. in the human body, shaped in such a way of intermediates and end-products.
One of his approaches is to use that only molecules with complementary
‘isotopic labelling’ to make it easier to structures are able to fit. BIG BUSINESS
differentiate between different regions While introducing isotopic labels is
of these large complex biomolecules. The highly complex structures of many a powerful tool to gain more structural
This technique has been so successful saccharides make standard NMR information on molecules by NMR,
that it has been commercialised by his techniques very challenging to use. introducing isotopes is a challenging
company, Omicron Biochemicals Inc., Professor Serianni’s group has found problem, spanning both synthetic
which provides services to researchers a way to overcome this limitation by and biological chemistry. Fortunately,
around the world. developing a range of new methods Professor Serianni and his team have
capable of introducing isotopic labels developed a suite of methods that

22 www.researchoutreach.org www.researchoutreach.org 23
The University of Notre Dame and Omicron Inc. work in
Q&A of furanosyl rings, such as those found in
DNA and RNA, appear promising; this work
transcends typical JHH analyses, as first applied
and in this regard NMR still reigns supreme.
Information on solution conformational
equilibria and dynamics evolves from
What are the most important molecular by Altona, Sundaralingam and others, and quantitative studies of different types of
parallel, utilising complementary approaches to push the limits structures you have been able to
elucidate using your techniques?
offers the potential to characterise their
conformational equilibria in greater detail and
NMR parameters, giving for example a
wealth of data on motions occurring on

of isotopic labelling and the applications of labelling to solving We have focused our attention on the
multiple structural elements in saccharides
with greater reliability than has been possible
for the past 40 years.
different time scales. These equilibria and
dynamics properties are often closely

important problems in chemistry and biochemistry that collectively comprise their structures.
The motivation is that, if we can develop What are the big challenges ahead in 3D
associated with biological function.

more quantitative experimental tools to structural determination? Did you face any difficulties creating
characterise these elements in solution, The assembly of larger oligosaccharides this spin-out company from your
have transformed the possibilities worldwide, enabling other researchers In the future, Professor Serianni these tools can be applied generally to containing site-specific or multiple labelling fundamental university-based research?
for the types of compounds that to purchase isotopically-labelled is optimistic that the innovative any structure, that is, we seek general with 13C and/or other biologically relevant Omicron Biochemicals Inc. was founded
applicability and thus greater impact. The isotopes presents significant challenges (in in 1982 at a time when faculty-inspired
can be precisely isotopically labelled compounds for use in their own work. approaches pioneered in the Notre
research questions are fundamental so contrast, uniform 13C labelling is currently companies were less common and less
at single sites, multiple sites, Dame Lab will lead to new spin-out that their potential impact can be broad. reasonably easy to accomplish using biological accepted in academic circles than they are
or uniformly labelled. The labs at both Notre Dame and companies able to exploit these Specifically, we aim to develop more methods but often leads to NMR spectral today. In practice, founding and sustaining
Omicron now work in parallel, utilising findings and apply them to solve detailed NMR-based models of many of complexity that resists analysis). Unlike a company while functioning largely as a
These approaches are currently being different approaches to push the specific problems that impact human the key mobile conformational elements oligopeptide and oligonucleotide synthesis, faculty member has proven challenging
found in saccharides, which include: (a) an automated instrument does not yet exist not in a technical sense, but rather in a
used to tackle fundamental chemical limits of isotopic labelling and the health and well-being.
O-glycosidic linkages in oligosaccharides; in the commercial sector to achieve assembly social-psychological sense – the age-old
problems in the Notre Dame laboratory applications of labelled saccharides (b) exocyclic hydroxymethyl group in high yields, although people such as question of which master do you serve?
– the same research location that led to address chemical, biochemical conformation; (c) N-acetyl side-chain Seeberger, Wong, Demchenko and others It is important to answer this question
to the development and expansion and biomedical problems. Without this conformation; (d) O-acetyl side-chain have been working to solve this problem. In clearly, to be self-aware and cognizant of
of Omicron Biochemicals, Inc. The work synergistic effort, tackling fundamental conformation; (e) hydroxyl group addition, having the ability to incorporate the importance of answering this question
conformation; and (f) furanose and pyranose labelled oligosaccharides into proteins (the honestly. Omicron was founded for two
done in the Omicron research facility problems encountered in saccharide
ring conformation. We have been frustrated latter either labelled or unlabelled) to generate main reasons: (1) there was a void in the
is somewhat different though, instead isotope labelling would have been with conventional NOE-based and simple chemically pure glycoproteins is still a major scientific community that the company
focusing exclusively on saccharide difficult, and the core technologies J-based methods to characterise these challenge; this problem needs to be solved filled by widening the range of compounds
isotopic synthesis using chemical, underpinning Omicron would never behaviours because they often lead to if we want to fully exploit heteronuclear NMR that could be labelled in an affordable
biochemical and biological methods. have been developed or would have generally unsatisfying solutions. This and other methods in conjunction with stable manner and on scales that enabled diverse
situation has led to an over-reliance on isotopes to interrogate their structures, applications; and (2) the company serves
This work has had an enormous impact been developed more slowly. MD simulation and related methods to conformational features, time-dependent as a key research resource for academic
assess these behaviours, yet experimental motions (dynamics), and biological functions. studies at Notre Dame that require access
validation of MD is weak. We contend to labelled compounds, without which the

Behind the Bench


that a more holistic treatment of NMR What are some of the advantages of using projects would be difficult if not impossible
J-couplings, which are highly abundant NMR for structural determination? to undertake in a timely manner. Any
in saccharides, is a potential solution to Nowadays, techniques such as mass success I may have achieved in academic
this problem, and recent studies using spectrometry (MS) have taken some of the research I attribute in significant measure
circular statistics in conjunction with DFT wind out of NMR, being far more sensitive to the unique opportunities offered by
appear to provide conformational models and thus amenable to determinations of Omicron as a partner in the work.
that can be compared directly to those primary saccharide structure when sample

Professor Anthony Serianni derived from MD. One of our core research
goals is to parameterise all biologically
relevant O-glycosidic linkages to enable
amounts are limited. Unlike for proteins, X-ray
crystallography has not proven as generally
useful for saccharide structure work because
Do you think it will become more
common in the future to see spin-out
companies developing from university
studies of their conformational behaviours obtaining high quality crystals of saccharides, research groups?
E: Anthony.S.Serianni.1@nd.edu T: +1 574 631 7807 W: http://www.nd.edu/~aseriann in simple and complex structures. This especially oligosaccharides, has proven to Yes, I do. Science, or specifically the
work hinges on the ability to label target be challenging and unpredictable. Neither conduct of science, is becoming
molecules with 13C at one or more sites to MS nor crystallography, however, provide increasingly codified. There is significant
allow measurements of JCC values. Recent information on saccharide solution behaviour, outsourcing of scientific work in most labs,
expansions of this approach to studies the biologically relevant state in many cases, and this trend is likely to continue over time.
Research Objectives Collaborators Bio
If you need to express a protein, you hire
Prof Serianni’s research interests • Ian Carmichael Anthony Serianni received a BS a company to do it. Scientific “kits” can be
include methods development for (University of Notre Dame) in Biochemistry from Albright College, purchased to expedite specific kinds of lab
site-specific labelling of carbohydrates, • Wenhui Zhang PA. He pursued graduate studies at work that would have taken considerable
conformational studies of simple and (University of Notre Dame) Michigan State University, earning a time and treasure previously. Perhaps
complex carbohydrates related to the • Allen G Oliver PhD in 1980. He later moved to Cornell equally important is that doing basic
research might be less costly in a company
N-glycans of human glycoproteins (University of Notre Dame) University for postdoctoral training, and
environment than in an academic one,
by nuclear magnetic resonance, • Jaroslav Zajicek in 1982, joined the University of Notre indirect costs being what they are. In the
applications of molecular orbital theory (University of Notre Dame) Dame, where he is currently Professor future, I would not be surprised if federal
to aid in the interpretation of NMR • John G Duman of Chemistry and Biochemistry. funding agencies increase their research
parameters, and structure-function (University of Notre Dame) support for companies engaging not only
studies of non-enzymic protein • Robert Woods Contact in applied research, but also in research at
(University of Georgia) Anthony S Serianni the fundamental level. Should this come
glycation.
to pass, academic institutions will need to
• Paul Bondo (Omicron) Professor of Chemistry & Biochemistry redefine their relationships and regulations
Funding • Shikai Zhao (Omicron) Department of Chemistry with respect to faculty entrepreneurs to
A hypersurface showing the torsional dependencies of the trans-glycoside J-coupling, 3JH1’,C2, as
National Science Foundation USA • Qingfeng Pan (Omicron) and Biochemistry determined by DFT for an αMan-(1→2)-αMan linkage like that between residues 5’ and 6’ in the ensure that the core values of both entities
(NSF USA) University of Notre Dame, Notre Dame hexasaccharide shown in Scheme 1 (A). This 3JCOCH value depends primarily on the H1’–C1’–O1’–C2 are protected and potential negative
IN 46556 – 5670, USA torsion angle (φ), with only a minor dependence on the C1’–O1’–C2–H2 torsion angle (ψ). impacts on these values minimised.

24 www.researchoutreach.org www.researchoutreach.org 25
Physical Sciences ︱ Professor Connie Lu

Configuring new bonds Decreasing M-Cr bond order

between first-row
28
25 26 27
Ni
Mn Fe Co

transition metals 24

Cr
24

Cr
24

Cr
24

Cr
Transition metals are some of the B.O.= 5 3 2 1
most important elements in the
Periodic Table for their wealth of
applications, spanning catalysis
to biology. The rich chemistry of molecules composed of ten or more Building metal-metal bonds can be like building blocks – chemical bonding to chromium (Cr)
can change from quintuple to single by varying the other light transition metal partner.
the transition metals arises from atoms. Ligands can be diverse not just
their remarkable ability to form in their chemical structure, but also in
multiple chemical bonds, a process how they attach to the metal centre. Professor Lu wants to find ways to exploit
that is still not fully understood
the properties of the more common light
Some ligands just bind directly to the
and remains a major challenge in metal whereas others bind through
fundamental chemistry. Professor
Connie Lu at the University of
multiple sites on the ligand, or in the
case of metal complexes with more than
transition metals, to replace their heavier,
Minnesota has been tackling this
question by synthesising the first
one metal centre, the ligands can act as scarcer counterparts
a bridge between the centres by binding
mixed-metal complex containing the two metals together. synthesis and carbon dioxide activation, This is why Professor Lu wants to
only the first-row transition metals
an important step in the development find ways to exploit the properties
to explore the fundamental nature
It is the variety and the complexity of this of sustainable energy technologies. of the more common light transition
of a chemical bond.
chemical behaviour that makes Professor metals, to replace their heavier,
Connie Lu at the University of Minnesota DOUBLE-DECKER METALS scarcer counterparts.

T
so fascinated by transition metals and Professor Lu’s research predominantly
he transition metals are a series their associated ligands. With her focuses on the lighter transition metals. One series of complexes that Professor
of elements mostly located in research group, she has designed over At present, many industrial processes Lu’s group have been making are
the middle of the Periodic Table. fifty new metal-ligand complexes, with that rely on catalysts make use of the dicobalt complexes, two cobalt centres
This includes elements such as cobalt, iron, a variety of different metal centres. heavier transition metal elements. joined together by some unusual ligands,
and manganese. What makes transition Now, she wants to use this knowledge However, the heavier transition metals also designed by her group, called
metals so interesting, and gives rise to the not just to address fundamental are significantly less abundant on Earth ‘double-decker’ ligands. These ligands
thousands of different ways in which they questions in chemistry, but to design and there is the imminent danger of are named as such because they act
can react, is their electronic structure, or next-generation catalysts for chemical shortages of many of these elements. as scaffolds for stacking together two
the arrangement of the electrons in the metal-metal centres, allowing the metal
element. As chemical bonding is all about centres to form multiple bonds with each
electron sharing between two different other. The more bonds formed between
chemical species, the electronic structure two species, the shorter and stronger
of an element dictates how an element will the bond but such multiple bonding is
react with other species and how many and very rare between two metals of different
what type of chemical bonds it can form. kinds. The design and properties of
these ligands has allowed Professor Lu
Transition metals typically have a large to achieve several world-firsts by making
number of electrons available for a molecule with triple bonds between
chemical bonding, but also space to two different light transition metals,
receive electrons from possible ligands, iron and chromium and a quintuple bond
molecules which bind to the central between manganese and chromium.
metal atom to form the final metal While quintuple bonds are rare in
complex. These ligands can vary in size, Bimetallic complexes can also deliver "ready-made" bimetallic active sites onto a solid support, themselves, the manganese-chromium
from single atoms, to highly complex as shown for the metal-organic framework material, NU-1000. complex remains the only example of

26 www.researchoutreach.org www.researchoutreach.org 27
Behind the Bench
Professor Connie Lu
E: clu@umn.edu T: +1 612 625 6983 W: http://www1.chem.umn.edu/groups/lu/

Research Objectives Collaborators with Karl Wieghardt. In 2009, she


Professor Lu’s lab seeks to develop • Professor Laura Gagliardi, University began independent research at the
homogeneous catalysts for converting of Minnesota University of Minnesota, where she
abundant small molecules, such as • Dr Eckhard Bill, Max Planck Institute is currently an Associate Professor.
N2 and CO2, into useful chemical for Chemical Energy Conversion
feedstocks, such as ammonia and • Collaborators in the Inorganometallic Contact
methanol, respectively. The group is Catalyst Design Center, University of Professor Connie Lu
interested in creating, understanding Minnesota, http://www1.chem.umn. Laboratory of Inorganic Synthesis
and exploiting new chemical bonding. edu/icdc/ and Catalysis
University of Minnesota
Funding Bio 207 Pleasant St SE,
• National Science Foundation (NSF) Connie Lu received a BS in Chemistry Minneapolis, MN 55405
• US Department of Energy, Basic from MIT and a PhD from Caltech with USA
Energy Science Jonas Peters. She was a Humboldt
postdoctoral fellow at the Max-Planck-
Institute for Bioinorganic Chemistry

Q&A
a quintuple bond between two different The difficult conversion of nitrogen to silylamine, when catalysed by the dicobalt complex, can
metal centres. occur at room temperature and at ambient pressure of nitrogen. Theoretical calculations predict transition metals and main group Do you think your bimetallic
that the hardest step is the formation of the second N-Si bond, which is shown on the right.
elements, which are to the right on the catalysts will be scalable for
THE NITROGEN PROBLEM What allows the double decker Periodic table. This is a new, exciting industrial processes?
Making bonds between metal centres industry for drug manufacture as well in solid supports, that can later be used ligands to bring together two direction for us because we have found The bimetallic catalysts contain
of different transition metals is a as for agricultural usages and in water in catalysis. By using the bimetallic different metal centres? that nickel-gallium pairings make great specialised ligands, which will be
powerful tool for exploring the chemistry purification. The possibility of being molecules as a delivery vehicle for Transition metals have certain catalysts for hydrogenating CO2. We expensive to make for an industrial
and bonding of transition metals and able to use nitrogen, rather than more the metal centres, it should be possible preferred geometries for binding are curious about some of the heaviest process. Rather, these catalysts are
forming an extensive library of such polluting chemical synthesis routes, as to make a greater variety of catalytic ligands. We take advantage of the well- elements, the rare earth metals, which wonderful demonstrations of what
compounds is important to further our a way of manufacturing these chemicals supports and develop new systems that known fact that a single metal centre reside at the very bottom of the Periodic light transition metals can achieve
understanding of catalysis design and would be a huge development towards make use of the more abundant lighter often prefers to form a five-membered table. While our current ligands are too together. To be scalable, we will need
synthesis. However, such compounds more sustainable chemical synthesis. transition metals. By bringing together ring with ligands. Our double-decker small for these metals, we have designed cheaper methods to place two metals
are not so commonly found in nature, chemical identification techniques used ligand design scaffolds just the right new ligands which we hope will allow us together on a solid support and to find
whereas bimetallic complexes, where the LOOKING AHEAD in other areas of chemistry, Professor number of donor atoms such that to explore bonding in the nether regions a support that will preserve the unique
two metal centres are the same transition Given the success of Professor Lu’s Lu also hopes to further characterise both metals are each part of three of the Periodic table. bimetallic reactivity.
metal, are found in many enzymes, group at making many metal-metal the unique bonding in the compounds approximate pentagons. As I write this,
nature’s catalysts for biological reactions. compounds with a variety of transition synthesised in her group and develop I think it would fun to ask grade school Do you think that it will be possible What’s the greatest number of
metal species, the plan is to find other models to further our understanding of children to see how many irregular to replace all heavy transition metal chemical bonds you’ve been able to
Professor Lu has found that one of exciting applications of this chemistry. how different metals bond and interact. pentagons they can find in one of our catalysts with lighter metal catalysts? create between two metals?
the dicobalt species her group has The bimetallic molecules made by the molecules. Absolutely, it is just a matter of time. Five. Quintuple bonds are still quite
synthesised is an incredibly efficient group can be used to install the metals Note: These are irregular pentagons We all want sustainable catalysts, and rare and are only known for transition
catalyst in turning nitrogen (N2) to because the sides and angles are researchers all over the world are working metals. My collaborator Laura Gagliardi
N(SiMe3)3, an amide species. Nitrogen not all equal. to replace heavy, precious metals with has predicted that the maximum

Professor Lu has achieved several world-


is an incredibly inert species that makes lighter, earth-abundant ones for all types number of bonds between two metals
up most of our atmosphere so getting Do you think these ligands can be of catalytic applications. As a community, is six. Isolating a molecule with a
it to react to form new compounds
is very difficult. However, amines are
firsts by making a molecule with triple used for all transition metals and
pairings?
we are generating knowledge about how
to better control the properties of the
sextuple bond would be spectacular,
and it remains an exciting challenge
very valuable chemicals, with a global bonds between two different light We can use these ligands to study light transition metals. for synthetic chemists.

transition metals
market worth billions of dollars; they other pairings, for example between
are widely used in the pharmaceutical

28 www.researchoutreach.org www.researchoutreach.org 29
Physical Sciences ︱ Professor Evan Scannapieco

In search of supermassive black hole feedback


Professor Evan Scannapieco astronomers are able to examine how the material reaches the event horizon
and his team at Arizona these types of galaxies evolved over time. – some is ejected perpendicularly, in
State University have been both directions, from the core and out
investigating the puzzle of To compare to these observations, of the galaxy. These outpourings are
why the largest galaxies in theoretical models were developed that of gargantuan proportions and images
the universe, once the most predicted hierarchical galaxy formation from radio telescopes show trails larger
active, have become dormant – in which gravity collects material than the galaxies that host them.
and ceased to produce stars. together to form stars and solar systems,
They were one of the first to like our own. However, some parts of the Professor Scannapieco and his team
propose a mechanism that universe did not fit the existing models: used a mathematical model to propose
involved colossal feedback from the largest galaxies, once the most that the shock of the ejections from the
supermassive black holes at
the centre of the galaxies and
they set out to prove the theory
The largest galaxies, once the most
using the Cosmic Microwave active in star formation, had become
Background radiation as a tool.
dormant with older stars dying without
replacements being created

A
strophysicists deal with distances active in star formation, had become hot disks surrounding supermassive
that are so vast and timescales dormant with older stars dying without black holes can be felt in the Intergalactic
that are so long that they are replacements being created. In 2004, Medium. His team’s research suggested
difficult for humans to comprehend. Professor Scannapieco and his team set that the gasses and other material within
The enormity of these scales first came out to determine why this was the case. the IGM may be heated such that they
into view roughly 90 years ago through They proposed a physical model, backed are no longer capable of coalescing
the work of Henrietta Leavitt and Edwin by rigorous mathematics, that suggested under the influence of gravity to form
Hubble. Leavitt analysed special stars an intergalactic feedback mechanism stars. Professor Scannapieco refers
called Cephids and discovered that their was operating, associated with the to this effect as ‘AGN feedback’.
luminosities were directly related to the supermassive black holes discovered
periods of their pulsations. Hubble then at the centres of elliptical galaxies. In fact, the team’s equations focus
used this relation and the observed on an increase in temperature that
brightness of Cephids to measure the THE AGN FEEDBACK THEORY changes the entropy of the IGM,
distances to galaxies outside the Milky Nearly fourteen billion years have passed a thermodynamic measure of the
Way. He found that they are so distant since the Big Bang, the formation point availability of a system’s energy to do
that their light takes millions of years of the universe. During the intervening work. Their findings predict that the AGN
to reach the Earth. Now we know of time, galaxies have been created by feedback mechanism will increase the
galaxies whose light takes over 10 billion the accretion of material from the entropy above a critical value, making it
years to reach us, revealing them as they Intergalactic Medium (IGM), the tenuous impossible for affected galaxies to cool
appeared in the early universe. material that lies between galaxies. and form stars by gravitational accretion.
Innumerable galaxies have been formed, This matches the observed universe, as
A MATTER OF SCALE each containing countless stars. Some has now been shown by many research
The billions of galaxies that fill the galaxies have merged and formed Active groups, some of which have built on the
universe can be broadly grouped Galactic Nuclei (AGN) at their cores, 2004 model, and others of which have
into moderate-sized disks, like our which result in higher than expected employed independently-developed
own galaxy the Milky Way, and giant galaxy luminosities that do not come models in which AGN feedback
elliptical galaxies with typical stellar from the stars. operates more gradually.
masses that are more than ten times
greater. By comparing the more distant Theory suggests that each of these COSMIC MICROWAVES
galaxies, which are observed as they galaxies contains a supermassive black With this variety of AGN feedback
appeared long in the past, with the more hole surrounded by a hot disk that is models fitting the observations,
nearby galaxies, which are observed accumulating material from the galaxy Professor Scannapieco and his team
as they appear closer to the present, to be devoured by the black hole. Not all worked to develop a method to

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Behind the Bench
Professor Evan Scannapieco
E: evan.scannapieco@asu.edu T: +1 480 727 6788 W: http://scannapieco.asu.edu/

distinguish between them. The key


difference between these possible
Research Objectives • Prof Hugh Couchman at McMaster the Kavli Institute of Theoretical Physics
models is their predictions for the
Professor Scannapieco’s research focuses University in Canada in Santa Barbara. He moved to Arizona
increase in IGM temperature, caused on better understanding feedback State University (ASU) in 2007 and is now
by supermassive black hole feedback. processes in galaxy formation and the The papers in which we measure the an Associate Professor in the School
evolution of the elements across cosmic feedback were led by ASU graduate of Earth and Space Exploration.
Innovatively, the team decided to use time. student Alex Spacek, in collaboration
the Cosmic Microwave Background with myself, Dr Seth Cohen, Bhavin Joshi, Contact
Funding and Prof Phillip Mauskopf. Professor Evan Scannapieco
(CMB) radiation, a remnant from the
• National Science Foundation USA Arizona State University
Big Bang, to measure the impact of
(NSF USA) The PI of the TolTEC Camera is Grant School of Earth and Space Exploration
AGN feedback in its heating of the Wilson at UMass Amhurst, and the ASU PO Box 871404
IGM. The measurements relied upon Collaborators lead is Prof Phillip Mauskopf. Tempe, AZ 85287-1404
an established mechanism called the The original papers we wrote on the topic USA
Thermal Sunyaev–Zel’dovich effect. were in collaboration with: Bio
When photons of electromagnetic • Prof S. Peng Oh at the University Professor Evan Scannapieco studied at
of California, Santa Barbara Harvard University and the University of
radiation, like rays of light or microwaves,
• Prof Robert J. Thacker at Saint Mary’s California, Berkeley and then worked as a
pass through a region containing University in Canada postdoc at Arcetri Observatory in Italy and
higher temperature gasses, some of the
photons interact with the gaseous atoms

Q&A
and cause electrons to gain energy and essential component in our modern structures in the universe do in fact
emit photons of a higher frequency. understanding of how galaxies form. form hierarchically. While the most
This results in a shift in the wavelength At the same time, there are many massive galaxies were the first to stop
of the CMB over what is expected. It is Map of the logarithm of the Thermal Sunyaev-Zel’dovich effect. The large panel is 1.1° on a side and The feedback hypothesis was different points of view on how this forming stars, as more time went by
these changes that can be measured, is generated from a simulation including AGN feedback. The smaller panel is 0.55° on a side and is very innovative at the time it was feedback may have played out in detail. they continued to group together into
compared with the ‘normal’ CMB and generated from a simulation without AGN feedback. Both maps are for measurements with frequencies proposed. How did you reach the Thermal Sunyaev–Zel’dovich effect even larger structures called galaxy
well below 160 GHz. The AGN feedback simulation has a higher average Themal Sunyaev-Zel’dovich
then, using a mathematical model, conclusion that AGN feedback measurements are one of the main tools groups and galaxy clusters. Today,
effect signal, which is also smoothed out on the smallest scales. Originally published in ‘Measuring AGN
converted into estimates of the thermal Feedback with the Sunyaev-Zel'dovich Effect’, The Astrophysical Journal, Volume 678, Issue 2, article id. was a possible reason as to why we have in constraining this process. the largest galaxy clusters contain
energy of the IGM. 674-685, pp. (2008) https://doi.org/10.1086/528948 © AAS. Reproduced with permission. giant elliptical galaxies might be thousands of galaxies, swarming
dormant? Using the Thermal Sunyaev–Zel’dovich around each other like bees.
One way that was proposed to do this We had two big hints. The first was that effect to measure the energy levels
was to examine the Thermal Sunyaev– Professor Scannapieco’s research the most massive galaxies stopped of the IGM has given credence to How has our understanding of the
forming stars first, a trend that is very the ‘feedback’ theory. How will you universe improved since the start
suggests that the gasses and other
Zel’dovich effect around active AGNs.
But this was problematic – AGNs hard to explain without a large energy confirm that your measurements of your research?
are accurate?
material within the IGM may be heated
source to suppress gas cooling. As an astrophysicist, I am fortunate
are rare and are so bright at many
The second was that the number of Our measurements are accurate but to be working in one of the most
wavelengths that their light contaminates
measurements of the microwave such that they are no longer capable of stars that elliptical galaxies contain
and the masses of their central black
still not very precise, because these
are difficult measurements at the limits
active areas of modern science.
Some of the most exciting results since
background. Instead, the team elected
to ‘stack’ many measurements of coalescing under the influence of gravity holes are closely related, suggesting
that the central black holes might have
of current instruments. Still, they are
already placing interesting constraints
2004 have included observations of
distant galaxies that appear as they
more common galaxies to enhance
the tiny signal and reduce extraneous to form stars a way of somehow “telling” their host
galaxies when to stop forming stars.
on feedback models. We are closely
working with groups building next
were during the universe’s infancy,
discoveries of earth-mass planets
noise. Professor Scannapieco chose generation instruments, like the TolTEC around other stars, and the detection
to examine massive elliptical galaxies Combining measurements from may be at work. Professor Scannapieco The supermassive black hole Camera, which will open up a new of gravity waves from merging neutron
that were dormant because of the AGN thousands of elliptical galaxies, and and his group are now working with the feedback mechanism has gained window on the history of gas heating stars and black holes.
feedback effect the theory suggested. correcting the measurements to allow team building the TolTEC Camera for traction since you and your team around large galaxies.
Two separate categories were chosen for contamination from other sources the Large Millimeter Telescope to make suggested it. What scientific
at two cosmic epochs corresponding to of light, delivered a result that was higher resolution measurements, which progress has been made due to the Can anything be salvaged from the
different distances from the observers. somewhat higher than suggested by they hope will prove to be definitive. interest you have triggered? apparently defunct hierarchical model
For the selected galaxies, data was hierarchical models that neglected the Through our work and those of others, of the universe?
used from two telescopes: the South effect of AGN feedback. These initial black hole feedback has become an The most massive gravitationally-bound
Pole Telescope in Antarctica, and the measurements made with existing
Atacama Cosmology Telescope in Chile. telescopes suggest that AGN feedback

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Physical Sciences ︱ Professor Mike Barnes

Offshore wind power’s big break


The World Energy Council projects funded by the European Union flows are maintained in the remainder
states that the capacity of since joining Manchester University of the network.
offshore wind generation in 1997. His current research into
installed globally was around circuit breakers forms part of a three- One of the key challenges to reliably
12,000 MW by the end of 2015 year research project funded by the operating this meshed configuration
with over 92 percent of these Engineering and Physical Sciences is how to stop current flowing in the
installations located in Research Council. event of a problem. Isolating DC with
European waters. This will circuit breakers is more complex than
require innovative solutions HARNESSING WIND POWER for AC. AC changes direction cyclically,
such as the work being done by A wind turbine can extract up to 60 falling to zero twice during a cycle
Professor Mike Barnes and his percent of the power from the wind which provides an ideal opportunity
team at the School of Electrical but because wind-speed varies, it is to interrupt current flow. However, DC
and Electronic Engineering at necessary to convert the alternating flows in one direction only so in the
Manchester University, on novel current (AC) output from the wind DC system, currents must be quickly
circuit breaker design for generator to direct current (DC) reduced to zero which requires a more
offshore power networks.
before converting it back to AC at complex breaker. The pertinence
Ultimately, this research could
a frequency that matches the onshore of Professor Barnes’ research is clear:
help onshore power networks

Current EU targets mean that by 2020,


to supply increased amounts
of electricity generated by
offshore wind turbines and
contribute to future low carbon the UK must generate 30 percent of its
electricity generation.
electricity demand from renewable sources

W
ind turbines are anticipated power network. Another advantage there is a pressing need to develop
to have a significant role to of this temporary conversion to DC responsive and economic circuit
play in the future energy mix. is its potential for power transmission breakers that quickly stop current
Electricity generated from renewable over greater distances with lower cost flowing if a fault develops within a
sources currently accounts for around 25 than is possible for an AC system. DC system without detriment to the
percent of UK electricity demand. Current This combined with the configuration wider network.
EU targets mean that by 2020, the UK of the power system are important
must generate 30 percent of its electricity considerations if turbines are to be IMPROVING EXISTING PROVISION
demand from renewable sources. located at greater distances offshore Should a fault develop within the DC
Expansion of the UK’s offshore wind in future. power network, it is necessary to limit
capacity has been proposed as one means the flow of current as quickly as possible
of achieving this target. Development Conventional “point-to-point” networks to prevent other parts of the network
of new and improvement of existing involve each offshore wind generator operating beyond their design
technology is required to support this being connected directly to the power parameters. This is currently achieved
proposed growth. network onshore. With an increased using AC circuit breakers which may
amount of installations, this method isolate the entire DC system leading
The research being undertaken by is anticipated to be prohibited by cost to power loss. This would mean that
Professor Barnes and colleagues could and technology limitations and therefore if a future wind installation comprising
help in achieving this target. They aim unsuitable to meet planned future of a network of five wind farms was
to improve circuit breakers for offshore expansion. The alternative option being operating and a connection to one farm
wind installations that could facilitate explored relies upon the DC component developed a fault, all five would have
greater flows of energy from increasing of the network comprising a “meshed” to be isolated and no power would flow
distances offshore whilst ensuring the grid configuration where connected wind from the four working systems. The
protection of existing power networks farms share pathways to the AC converter UK power network operates to certain
onshore. Professor Barnes has been onshore. If a fault develops in the DC supply quality standards that state that
heavily involved in several large meshed network, discrete parts of the the maximum power loss the network
collaborative wind energy research network can be isolated whilst power can bear is 1800MW. Presently, any such

34 www.researchoutreach.org www.researchoutreach.org 35
Behind the Bench
Lost transmission
Transformer
Rectifier Inverter
DC
AC

Professor Mike Barnes


Fault E: mike.barnes@manchester.ac.uk T: +44 (0) 161 306 4798
W: http://www.research.manchester.ac.uk/portal/en/researchers/mike-barnes(9484b24e-0a22-44a0-
AC bb9f-02083d354ce0).html

Research Objectives Bio Contact


Without a circuit breaker (above), a fault Professor Barnes and his team are Mike Barnes graduated with BEng Prof Mike Barnes
prevents the flow of current acrosss the whole developing a smaller, faster current (’93) and PhD (’98) degrees from the School of Electrical & Electronic
circuit. With a DC circuit breaker (below), a fault
can be isolated, allowing current to flow from
Transmission lost Detection and breaker for offshore use to aid the University of Warwick, Coventry, UK. Engineering
the remaining wind farms. Isolation integration of offshore wind farms into He became a Lecturer at the University University of Manchester
reduced the National Grid. of Manchester Institute of Science Oxford Rd
Transformer and Technology (UMIST, now merged Manchester
Rectifier Inverter Funding with The University of Manchester), M13 9PL
DC EPSRC Manchester, UK in 1997, where he UK
AC is currently a Professor. His research
Collaborators covers the field of power electronics
• GE Grid Solutions systems.
Fault • Scottish and Southern Energy
Networks
DC Circuit Breakers AC

Q&A
How did you become interested companies to make the necessary long- Europe is leading in the development
in power networks? term investment in the UK. of offshore wind – where else in the
losses from existing offshore wind farms
are within network operating limits
There is a pressing need to develop What modern electronics can do
is amazing: from healthcare to Your research has led to patentable
world do you see potential?
China, Japan, India and North America
but with up to 30,000MW of electricity responsive and economic circuit breakers entertainment to transportation. results. How close are these to being are also active in this area and we
potentially being sourced from offshore As anyone who has ever been stuck put into practice? expect to see rapid development
wind in future, isolating larger capacities for DC systems with a low battery on their smartphone Our ideas are being developed by people of the technology by them.
could exceed this maximum. This knows, getting power to all this is around the world. China, Korea and
would lead to severe impacts and, fundamental. I just got fascinated by even NASA are working on some of the What are the next steps
without mitigation technology, could Professor Barnes’ research team will also time. Solid-state breakers that use the challenge of trying to achieve this concepts, and our work is being used for your research?
potentially cause blackouts over parts investigate the potential of fault current semiconductors technology are an sustainably for future generations. Plus, by people active in this area. However, We will continue to work with
of the UK electricity network. DC circuit limiters. These devices limit or slow alternative option; they operate more you get to work with some really cool we will only see these devices appearing manufacturers and utilities
breakers are commercially available the current increases that may occur if a quickly than mechanical breakers but and amazing technology and people. once we see large high-voltage DC in this area to look at the route
and may be used to manage faults that fault develops but have not been widely have higher losses which compromise networks emerging, which will be a few to commercialisation and at the
develop in the DC network. However, used on DC networks. The team will system efficiency. Hybrid systems Can the UK meet its target to supply years yet. However, before you put such implications of such equipment
to maintain power flows, these need also consider the fundamental principles which use the best characteristics 30% of its electricity demand from equipment on the network, there are on existing hardware.
to isolate the affected area within two of physics that underpin the design of of mechanical and solid-state breakers renewable sources by 2020? several years of writing guidelines and
to five milliseconds. Currently available existing systems and components while show potential but are currently not In June this year, 50% of electrical specifications to ensure effective and safe
technology cannot achieve the fastest examining the materials from which sufficiently reactive. The outcome of power was produced from renewables use of such installations – so the research
of these constraints and so a new current breakers are composed with this research will be to propose novel for a short while. So the target of a has direct relevance even now.
development is needed. the aim of identifying desirable and and improved methods for circuit high proportion of renewable energy is
unwanted attributes of each. breaking on future DC networks achievable – but it requires a long-term In June this year, 50% of [the UK’s]
APPROACH TO THIS CHALLENGE
To improve circuit breaking within DC Circuit breaking within a DC power
which could in turn support increased
development of offshore wind.
strategy. That in turn means clear and
binding decisions by government on
electrical power was produced from
power systems, in addition to thoroughly system may be achieved mechanically our future energy plans to allow energy renewables for a short while
reviewing the different types of DC using switches. However, these are
circuit breaker currently available, currently limited by their operating

36 www.researchoutreach.org www.researchoutreach.org 37
Physical Sciences ︱ Dimitrios Pezaros & David Hutchison

Making the Internet a safer place


Back in May 2017, a huge investigators, such incidents could
cyberattack crippled several
of the largest digital networks
Situation Awareness added to our be better controlled if resilience
management were in future deployed
in the UK and US, paralysing resilience framework can help the fight in networks, acting more intelligently
over two hundred thousand to detect the onset of attacks, assisted
computers. To combat such against damaging cyberattacks by situation awareness information.
threats Dimitrios Pezaros,
Senior Lecturer at the University UNITED WE STAND; DIVIDED
of Glasgow, and David WE FALL
Hutchison, Distinguished The SAI2 researchers were concerned
Professor of Computing at that cyber security was too reliant on the
Lancaster University, launched static defence of individual end devices.
SAI2 (A Situation-Aware The focus should be on protecting the
Information Infrastructure), whole networked system, and constantly
a research project aimed at
checking for intrusions.
developing new technologies
to fight against cyber threats.
Think about the setup in a typical
household – a desktop, a laptop, a tablet

C
and a smartphone. All these devices can
yber attacks are becoming more be fitted with protective technology like
and more common, finding their antivirus software. But in case of a threat,
way into the headlines every each will mind its own digital business.
couple of months. The incident in May If a hacker fails to get past the security
2017 was a fairly typical but high impact running on a desktop, it doesn’t mean
ransomware attack. Software called he or she will be just as unlucky when
WannaCry infected several organisations’ attacking a laptop. One way around
internal computer networks, using the this is to use a home gateway equipped
EternalBlue tool, or ‘exploit’, to install with a firewall that is supposed to
rogue software on unpatched and protect the whole network. But the
vulnerable computers. The vulnerability firewall’s rules – what it does and does
was also used to spread the WannaCry not recognise as a threat – are usually
code from one computer to another. static and thus can’t adapt intelligently
On each infected computer a ransom to break-ins on the network or attacks it
was demanded for putting the rightful has not encountered before. When we
users back in control.Another widely multiply this by thousands of computers
publicised cyberattack hit Dyn, a Domain connected into one of the largest
Name System (DNS) provider, in 2016. networks of the world, the problem
A ‘botnet’ was formed by infecting large gets significantly worse.
numbers of easily-hacked networked
IoT (Internet of Things) devices such as That’s why the SAI2 team focused
IP cameras, printers and other everyday on building a security system that
gadgets which were used to launch a integrates different sources of
Distributed Denial-of-Service (DDoS) information like operators’ warnings
attack on the Dyn servers. This led to about cyber threats, social media news
many major Internet platforms that are feeds, or indeed any relevant contextual
dependent on Dyn becoming unavailable information, as well as conventional
to huge numbers of their users. network traffic packet traces.

According to the Situation-Aware A computer network is frequently


Information Infrastructure (SAI2) referred to as the information highway,

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A framework for resilience in networked systems
Behind the Bench
ose Professor David Dr Dimitrios
n
De Hutchison Pezaros

ag
d
en t

Di
E: d.hutchison@lancaster.ac.uk T: +44 (0)1524 510331 W: https://www.gla.ac.uk/schools/computing/staff/dimitriospezaros/

ec
De
carrying bits of data travelling W: www.research.lancs.ac.uk/portal/en/people/david-hutchison

t
in both directions between
connected devices at extremely Research Objectives Collaborators David Hutchison is Distinguished Professor
high speeds, and as with a Prof Hutchison and Dr Pezaros work on Lancaster University: Andreas Mauthe, of Computing at Lancaster University and
real highway there’s much that improving cybersecurity. In particular, Angelos Marnerides, Noor Shirazi, & Steven has been doing computer network research
can be inferred by measuring their research aims to give networks Simpson. University of Glasgow: Joemon for more than 25 years. He now focuses
the traffic. What the SAI2 team better abilities to detect and respond to Jose, Long Chen, & Simon Jouet largely on resilient and secure networking,
cyberattacks and other challenges. with interests in the Future Internet and

Re
proposed was algorithms and
Bio also the protection of critical infrastructures
er
tools for detecting anomalies in Funding Dimitrios Pezaros, CEng, SMIEEE, SMACM, including utilities and industrial control

m
the measured traffic, and then • UK Engineering and Physical Sciences is Senior Lecturer (Associate Professor) systems.
v
reacting to such anomalies in short di

e
o
Research Council (EPSRC) TI3 Project EP/ at the School of Computing Science,
timescales. It sounds simple, but c ate L026015/1: Situation Awareness. University of Glasgow. His research focuses Contact
Re • European Cooperation in Science and on the resilient and efficient operation of Prof David Hutchison

Re
the real challenge lies in deciding
how to respond to anomalies. The fin Technology (COST) Action CA15127: virtualised and software-defined networked Lancaster University, InfoLab21
RECODIS on Resilient Communication infrastructures. He holds BSc and PhD Lancaster, LA1 4WA
SAI2 researchers have been better able e Services. degrees in Computer Science from UK
to spot when something suspicious Lancaster University, UK.
is going on by analysing network

Q&A
data traffic patterns alongside global
information feeds from social media How does your Situation-Aware amplification attacks can take significant
network architecture work? parts of the infrastructure offline for
(e.g., Twitter) and news (e.g., Reuters)
Situation Awareness is facilitated through long periods of time, preventing users
sources. However, to accomplish this
What first got you interested in a novel network architecture that makes from accessing online services but also
and at the same time feed any alerts cyber security and resilience? the network’s main data-forwarding plane from running their own businesses over
back to the network infrastructure in
short timescales, they decided to revisit
Resilience management can use The realisation that computer networks
increasingly become part of the national
programmable. This is achieved through
each switch in the network supporting
the cloud.

the fundamental packet switching Situation Awareness to help make better critical infrastructures, and are therefore
too important to fail. We have been
a minimal, performance-bound instruction
set. Based on this, centrally-controlled,
What, in your opinion, will
perpetrators do to defeat future
remediation and recovery decisions
mechanisms of the network. Doing so
working in the areas of network and minimal programs can be installed on cybersecurity systems like those
for large networks that transmit data at
service management for years, and the switches along the data path to you’re working on?
rates of hundreds of Gigabits per second we are bringing this know-how into an enable high-speed, adaptive functionality Over the years, there has been the
and multiplex traffic for millions of users LOOKING OUTSIDE and where those people did so, etc. emerging area requiring holistic solutions alongside packet switching. Using this typical cat-and-mouse game between
over large, geo-distributed data centres While the term ‘cloud computing’ This is all invaluable information when to enable emergent properties such as novel architecture, we have demonstrated perpetrators and defence systems
poses significant technical challenges. sounds intangible, the reality is our it comes to dealing with and assessing reliability and resilience of large-scale several use-cases of monitoring and control where the latter have been developed
So, the SAI2 team developed a novel, photos, emails, videos or medical crises. Suspicious activity will appear in networked systems. Actually, what we functionality such as exponential weighted or amended in response to a new
programmable switching architecture records have to be physically stored Twitter data patterns like ripples in the work on is the resilience of networked mean average computation on every switch attack, and new attacks are being
systems, which includes cybersecurity along the data path for normal behaviour developed to exploit previously unknown
that can natively incorporate monitoring on servers located somewhere. Clouds water. So, the SAI2 team went on to build
but goes beyond it to respond to profiling (a prerequisite for enabling vulnerabilities. The work in this project
and adaptive control intelligence as part and any critical infrastructure will be algorithms that model such news feeds cyberattacks (and other disruptive anomaly detection), as well as collaborative strives to break this endless cycle of
of the main packet forwarding operation subjected to challenges including natural into their cyber security systems. In this challenges such as natural disasters) and pushback for distributed, denial of service events by making the infrastructure
of the network infrastructure. This way, disasters and a variety of operational way, computer networks of the future rapidly attempt to remediate and recover attack remediation. adaptive, able to learn from its own
Hutchison, Pezaros and their colleagues failures as well as cyber attacks. The will know what’s happening around the normal operation of the system. past behaviour, and to harness as much
designed a cyber security system that is SAI2 investigators apply a resilience them as well as inside the network and How can a cyberattack affect information as possible to try and predict
How can the Situation-Aware a regular person? the onset of adversarial events. This
aware of what’s going on in the entirety management framework to protect can react accordingly. Does this mean
information infrastructure benefit us, Cyberattacks can deprive users from way, defence against cyber-attacks does
of the network it protects, and can react such networked systems, assisted by they will become self-aware? No, they
the end users? accessing their data on a physical machine not depend on static knowledge that
according to the temporal operational situational awareness information from won’t. But the idea is that future networks A Situation-Aware information or over the cloud, and from always- can only protect against a certain set
conditions and incidents as and when external sources including social media. will exhibit other properties like self- infrastructure should aim at making the on connectivity which is increasingly of vulnerabilities but rather it evolves
they unfold. But knowing what’s going management and self-adaptation which underlying interconnection medium considered vital. Cyber incidents where together with the operation of the
on inside the network was only the Of all social media platforms, ultimately will make them more resilient even more transparent to the end-user attackers encrypt the victim’s data and networked infrastructure.
first step in building a situation-aware Twitter is certainly one of the most and reliable: properties which will benefit by minimising down-time and through subsequently ask for ransom in order
rapid re-engineering of its operation to decrypt it are becoming increasingly
infrastructure. The next logical step was accommodating to researchers – its us all.
at the onset of adversarial events, while popular. At the same time, attacks on the
to equip the network with the ability data is easily obtainable: how many offering uninterrupted services to networked infrastructure can have wider
to understand, to an appropriate extent, people tweeted a particular message; its end users. and more costly effects. Volume-based
the outside world as well. how many used a given hashtag; when

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Thought Leader

CPHA: The heart of


Canadian public health
Health related issues, such as diabetes, heart disease or obesity, can often be hugely influenced by public health initiatives.
In her role as Chair of the Canadian Public Health Association (CPHA), Dr Suzanne Jackson champions a public health
perspective on important public policy discussions that impact the health and well-being of Canadians. She spoke to us
about CPHA’s influence since its foundation – both the positives and negatives – before highlighting where public health
policy needs to focus its attention in the coming months and years.

P
ublic health affects everybody – it’s a diverse range of roles and professions CPHA also runs some projects under
inescapable but paramount. Recent in public health – nurses, physicians, contract to government and others to
societal changes seen in the UK inspectors, nutritionists, dentists, health create resources or training opportunities
formed from public health policy include promoters and researchers. for public health workers. We serve as
the five-a-day healthy eating initiative, the the home for the Canadian Journal of
smoking ban and the sugar tax. The Board defined a strategic vision for Public Health and we communicate with
CPHA in 2015 that represents an overview our members regularly about events,
In Canada, the Canadian Public Health of what we do. Two goals are related to new reports and publications, and jobs
Association (CPHA) is the independent the organisation (engaged membership, in the field of public health in Canada.
national voice and trusted advocate financial stability), and the remaining
for public health, speaking up for four goals relate to our main role. The CPHA marked its centenary
people and populations to all levels of These include: in 2010. What impact do you think
government. Through its work, CPHA 1 National, independent evidence-based the organisation has had on Canadian
has operated untiringly to improve voice for public health in Canada public health since it was founded?
Canadian public health, having previously 2 Represent the public health Are there any achievements that really
advocated for national health insurance community’s interests in public health stand out for you?
in the late 1930s, fluoridation in the system renewal I have always been proud of CPHA for
early 1970s, and establishment of the 3 Convenor of partners to identify taking positions on public health at the
first national HIV/AIDS education and solutions to public health issues leading edge. As a worker in the system, it the first national HIV/AIDS education Careful policy research about the level of example, the Chief Public Health Officer’s
awareness programme in the 1980s. 4 Inspire and motivate change in support was great to see the leadership offered by and awareness programme. evidence in the literature in relation to Report in 2015 focused on alcohol
of health equity taking a stand on issues ahead of what the identifying the key components of a and our position paper was referred
Dr Suzanne Jackson has worked in the rest of the field was doing. For example, CPHA also held positions on the dangers policy issue is very important. CPHA to several times.
public health field since the early 1980s We run a big conference every year we are making an important contribution of smoking and second-hand smoke prides itself in providing timely, evidence-
and is the current Chair of CPHA (2017– to exchange the latest information about to what to do about climate change. that added to the pressures to change informed public health guidance and Our 2014 recommendations to
18). In her career, she has seen numerous what is going on in public health, we policy felt by all levels of government. perspectives to public health professionals the House of Commons’ Standing
positive global public health changes but is convene a national table for all provincial My involvement in the field goes back However, the way I remember it is that and policy makers. It ensures that its Committee on Health regarding
aware that more needs to be done. She and territorial public health associations to the mid-80s when CPHA co-sponsored some very committed and brave Medical positions and statements can be backed e-cigarettes were repeated practically
sat down with us at Research Outreach to to meet several times a year (mostly the Ottawa Charter conference with Officers of Health in Ottawa and Toronto up by the best available evidence. We verbatim in the Committee’s report.
discuss this, and more, in further detail. by teleconference), we research policy WHO in 1986. Since then, this has led to persuaded their local Boards of Health also re-evaluate our positions periodically These recommendations are echoed
issues of interest to our membership, a remarkable 30 years of global attention to adopt innovative by-laws, serving to ensure that we do not become in the current Bill S-5 in the Senate.
Hello Suzanne! Can you give us an and we also develop position statements to health promotion following the same as members of CPHA and leaders in dogmatic and that we are informed
overview of what the CPHA does? which form the basis of our advocacy guidelines – no other field can argue public health in the country. The anti- by the most recent evidence. Our 2016 recommendations to the Task
CPHA is primarily a member-driven to government departments, media such global consistency. Not only that, smoking in public places by-laws were Force on the Legalisation and Regulation
organisation. Its members represent and other organisations. but, also in 1986, CPHA established a remarkable public health achievement. An evidence-based approach is of Cannabis are clearly represented
Among many other major public health important for us to be a credible voice in the Task Force’s recommendations
milestones, CPHA notably advocated for public health in Canada and to to government.
for national health insurance in 1939, advocate for change to public policy
I have always been proud of the Canadian abortion in 1972, water fluoridation
in 1977, and against nuclear weapons
to the federal government. Although we cannot be sure of the extent
of our influence at other levels, I believe
Public Health Association for taking positions in 1982. What involvement does CPHA that CPHA papers and resources have
have in the development of public been used by public health officers across
on public health at the leading edge What is the importance of research health policy? the country to advocate for changing
in CPHA’s work? We have had some influence. For policies at the local public health unit

42 www.researchoutreach.org www.researchoutreach.org 43
Thought Leader

level. They have been used in the One of CPHA’s goals has been to policies at the provincial and municipal surveillance information to monitor the
preparation of media reports about health increase understanding that health levels. Given the federal involvement situation and evaluate progress.
issues in Canada. Media exposure affects is determined by many factors directly in Indigenous issues in Canada,
public opinion which, in turn, affects outside of the health care system. a clear policy should have a direct Finally, can you tell us what is it
politicians and policy makers. So, for example, living with violence, influence on decreasing violence towards about public health that interests
or in fear of violence. What are the Indigenous women. The policy would you personally?
As a specialist in health promotion, advantages of bringing factors outside have to be holistic and recognise the I really like that public health takes a
can you explain what is meant by the health care system to bear on the intergenerational trauma of residential population focus and tries to make sure
health promotion? What are the understanding of health? schools. It would also need to put in everyone is reached using public health
benefits of considering an issue from Realising that there are factors outside place other components that would measures (e.g. immunisations, nutrition,
a health promotion perspective? the health system that affect health helps be required to reduce structural or school health, healthy babies, tobacco
As per the Ottawa Charter, 1986, health to identify the policy changes needed system level violence, such as dealing legislation). I like the systems or structural
promotion is “the process of enabling to affect the greatest numbers of people with housing, water and sanitation, food approach to much of public health
people to increase control over their
health.” I see four main ‘hooks’ coming

I like the way public health goes beyond individual behaviour


from this definition and these guide
my teaching and practice.
1 Focus on determinants of health –
the factors that affect people’s health
change to look at the conditions that create health
are broad and include peace, clean
environment, resilient ecosystem,
education, income. This means that at the population level. Inequities security, youth health, employment successes (e.g. restaurant inspections,
health promoters focus on changing become clear and this is also important and income, and cultural connections. water monitoring, sanitary systems,
policy to affect such broad factors. This to recognise in policy. Looking upstream And very importantly, the policy process tobacco by-laws, seatbelt legislation).
was originally conceived as building keeps us from blaming people living should engage Indigenous peoples I like the way public health looks at the
healthy public policy, but it has now in difficult circumstances for their health in its formulation, so that further system causes of the causes and goes beyond
evolved into “whole of government” problems and steers us away from taking violence of exclusion from decision- individual behaviour change to look
policies and “health in all policy”. an individual behaviour change approach. making is not perpetuated. CPHA at the conditions that create health
This also forces attention on “creating is currently working with Indigenous and works at the policy level. I also like
supportive environments” and When other sectors recognise the leadership in Canada to work out how the values of equity, cultural sensitivity,
“intersectoral collaboration.” parts they play in creating unhealthy their perspectives can be included focusing upstream, environmental
2 Focus on the positive – health or healthy conditions, partnerships can in CPHA advocacy positions and concerns, participatory approaches,
promotion focuses on achieving emerge. So, for example, CPHA partners relationships. and the interest in evidence.
something positive – health – it is goal- with the Canadian Produce Marketing
oriented rather than problem or disease Dr Suzanne F. Jackson, Association to promote the consumption There is currently a growing opioid • For more information on CPHA – the
Chair, Canadian Public
oriented. Instead of looking at people Health Association of vegetables and fruits. crisis in Canada, which is resulting Canadian Journal of Public Health, their
as bundles of problems and deficits, in large numbers of overdose deaths. conference or the Association itself –
health promoters look at people as As mentioned in the previous What are CPHA’s strategies for dealing please visit their website at www.cpha.ca.
collections of strengths and assets. This required in health promotion from the tell us a bit more about this? How question, CPHA has drawn attention with this issue?
means using a “situational analysis” individual to family to community to important is it for the public health to the impact on health of living with As our position statement on the
rather than a “needs assessment” societal levels, many kinds of strategies community? violence, or in fear of violence. This Opioid Crisis states, we believe that
in programme planning as well as are required from health education, CPHA hosts Canada’s largest annual has been most notable in the case the current emphasis on changing
focusing on achieving goals framed community development, intersectoral public health conference to share current of missing and murdered Indigenous prescribing practices and disrupting
in a positive way. collaboration to building healthy research, promote best practices and women. If violence was clearly the availability of drugs are limited
3 Focus on participation – in order to public policies. Health promotion is improve health and well-being. The identified as a priority health issue strategies. These are interventions aimed
enable people to increase control over about affecting change at individual, conference is an important opportunity in federal policy, what difference do at the downstream impact of problematic
their health, they need to be involved community and societal levels and for public health workers and researchers you think that would make to violence substance use. CPHA is recommending
directly in the decisions that affect their there are many theories and strategies to meet, network and exchange views against Indigenous women in Canada? that Canadians address the underlying
health. This means using participatory guiding this work. on interventions and concepts that are Violence in all its forms is a key causes of problematic substance use
approaches to planning, evaluation and working. CPHA holds the conference in determinant of mental illness. Making such as trauma, racism, colonialism,
research. This means listening at the The benefits of considering an issue different parts of the country each year societies free from discriminatory criminalisation, and poverty. Dr Suzanne Jackson
individual level, using group consensus from a health promotion perspective is to make it easier for people in that area practices, bullying and other forms In addition, CPHA advocates for Canadian Public Health Association
methods at the community level, and that one considers a range of causes of to come and highlight achievements in of violence, promotes mental wellness. involvement of people with lived 404-1525, Carling Ave, Ottawa ON,
community development approaches the causes – one looks at what can be different parts of Canada. This year it is If we don’t address this issue, people will experience with opioids in discussions K1Z 8R9 Canada
and participatory decision-making achieved positively rather than reducing a being held in Halifax and next year it will still suffer unnecessarily from mental stress about the best approach to take; take
at the societal level. “Strengthening deficit, and a range of possible strategies be in Montreal. It keeps us connected to and illness. a harm reduction approach (e.g. more T: +1 (613) 725-3769
community action” was the original are considered. what is going on in all parts of the country safe consumption facilities in communities;
F: +1 (613) 725-9826
Ottawa Charter strategy. and it is good for inspiring the next If violence prevention is clearly identified make naloxone available over the
W: www.cpha.ca
4 Using multiple strategies at multiple In June, CPHA is hosting the Public generation of public health workers. as a priority health issue in federal counter); develop legislation to protect
levels – given the breadth of work Health 2017 conference. Could you policy, it sets a clear direction for other first responders to overdoses; strengthen

44 www.researchoutreach.org www.researchoutreach.org 45
Health & Medicine ︱ Professor Chris McMaster

A new class of
antibiotic drugs
M
Finding new classes of antibiotic ulti-drug resistant bacteria, currently in clinical trials, of which there
drugs could not only save human commonly known as superbugs, are less than 40, is a ‘me-too’ version of a
lives, but also greatly reduce kill over 700,000 people current antibiotic versus a known target.”
the healthcare costs related annually. However, more worryingly, this
to tackling bacteria resistant number is predicted to rise to over ten This highlights the need to develop
to currently available drugs. million by the year 2050. This would have entirely new classes of antibiotic drugs,
Professor Chris McMaster, massive repercussions, in terms of both which would be able to treat infections
director of the Cheminformatics the number of human lives lost and on caused by drug-resistant bacteria. Trying
Drug Discovery Lab at Dalhousie the world’s economy, which would lose to address this problem, Prof Chris
University in Halifax, Canada, several trillion dollars due to sickness McMaster and his team have developed
is developing a new class of and death of patients infected by these a new class of antibiotics that could help
antibiotics, while trying to bugs. Only a small handful of scientists treat infections.
overcome the many challenges are trying to develop new antibiotic drugs
associated with this particular that could counteract these superbugs – CHALLENGES OF THE FIELD
field of research – namely, the although many challenges are currently Despite the urgency and importance
limited sales of these drugs, the
slowing down progress. associated with developing new
lack of funding, and the greater
classes of antibiotics, this does not
focus on other pharmaceuticals.
THE NEED FOR NEW ANTIBIOTICS come without challenges. Several
Antibiotics are a type of pharmaceutical factors impair the introduction of new
drug that destroy microorganisms or antibiotics into the market, making it a
prevent them from growing. These are tortuous and difficult process.
generally used to treat or prevent a
variety of bacterial infections, including “A new class of antibiotic will likely be
pneumonias, tuberculosis, several the drug of last resort to treat patients
sexually transmitted diseases (STDs), and with multi-drug resistant infections
many others. implying that there will be limited use,

Antibiotics are generally classified


and hence limited sales,” said Prof
McMaster. “Second, the payers have
save a life,” said Prof
McMaster. “Contrast
New classes of antibiotics could save by an impaired
ability of the body to
based on a number of factors, including been able to pay pennies per treatment this situation to lives, entirely eradicating bacteria produce the hormone
their mechanism of action, the type for antibiotics for decades, and the anti-cancer drugs, insulin, resulting in
of bacteria they target, and chemical market feels there will be resistance to a where there are over resistant to current drugs abnormal metabolism
structure. While most doctors prescribe highly priced antibiotic.” 800 drugs currently of carbohydrates and
antibiotic drugs on a daily basis, some in clinical trials, many of which will have He said: “We landed on early-stage high glucose levels in the blood. Each
bacteria have become resistant to all Due to these issues related to sales and price points in the tens to hundreds of diabetic foot infections (DFIs) as having year, approximately 1.5% of diabetics
existing drugs, causing severe illness price of the drugs, research developing thousands of dollars per patient, and a large patient base with a high unmet develop what is termed diabetic foot
and death to a considerable amount of new antibiotics is often poorly funded. many of these drugs will extend life-span need, no currently approved antibiotic, ulcer infections (DFIs), which range from
people. This is ironic, as in contrast with other but not offer a cure.” and an expected high level of uptake relatively mild, to more problematic.
drugs that offer momentary relief from into the clinic and market. There is
Most antibiotics currently developed symptoms, or drugs that elongate the TREATING DIABETIC INFECTIONS also a dramatic increase in cost as For more severe infections, patients
to tackle these bacteria are based on lifespan of affected individuals, new To overcome the funding issues related DFIs become more severe allowing generally receive antibiotic therapy,
late generations of existing antibiotics. classes of antibiotics could actually to the assumption that new antibiotics for a reasonable price point to be yet approximately 50% of moderate
However, resistance to these drugs tends save lives, entirely eradicating bacteria will have low sales and a low price point, established for a new drug that could DFIs progress to more serious stages.
to develop quickly, due to individual resistant to current drugs. Prof McMaster chose to develop a new treat this condition”. This therefore comes with substantial
bacteria already having underlying class of antibiotics that would meet the healthcare costs related to further
mechanisms of resistance to similar “This conundrum is especially odd needs of at least 200,000 patients per ANTIBIOTICS AND DIABETES treatment or surgical amputations.
antibiotics. As Professor Chris McMaster considering that in many cases year, whose infections are hard to treat Diabetes is a disease that affects over Currently, no drugs on the market have
puts it himself: “Every single antibiotic antibiotics will cure an infection and using current antibiotics. 415 million people worldwide, caused been proven to successfully decrease

46 www.researchoutreach.org www.researchoutreach.org 47
Behind the Bench
LPS
Outer membrane

Inner membrane

Lipid A (10-14) Phospholipids (14-18) PlsBCXY Dr Christopher McMaster


HtrB E: Christopher.McMaster@Dal.Ca T: +1 (902) 494 3430 W: https://medicine.dal.ca/departments/
Haemolysin (12) HlyC MsbB department-sites/pharmacology/our-people/faculty/christopher-mcmaster.html
LpxD Acylhomoserine
lactones (4-16)
LpxA
O LuxI AinS
Biotin (7) BioCFH Research Objectives Bio Contact
ACP SCR Dr McMaster’s research focuses on
metabolic regulation with an eye
Dr Christopher McMaster received
both his BSc and PhD from the
Christopher McMaster, PhD
Carnegie and Rockefeller Professor and
Luminescence (14) toward the development of therapies University of Manitoba, later working Head
Lipoic acid (8) LipA LuxD for unmet medical needs in the as an Assistant Dean at Dalhousie Department of Pharmacology
infectious and inherited disease University. He currently works there Dalhousie University
FA synthase spaces. still, as the Carnegie and Rockefeller Canada
FabABDFGHIZ AasS(+ATP) Professor and Head of the Department
Funding of Pharmacology and Director of the
Canadian Institutes of Health Research Cheminformatics Drug Discovery
(CIHR) Lab at Dalhousie University in Halifax,
Acyl-ACP
ACP SH synthetase (≥4)
Canada.

Membrane-derived
oligosaccharides

Q&A
MdoH
AcpS AcpH Other known partners
private sector. The private sector looks to
make medicines that can make a profit,
by clinicians as DFIs are a disease
for which no current antibiotics are
SpoT, MukB, AidB, IscS, which makes sense. Most antibiotics are effective, have a large patient base,
SecA, TesA/B, YbgC, YiiD,
AccA, AceE/F, GlmU, PssA, ... Why is developing new classes of expected to be priced low and used little and a rapid increase in cost as the
apo-ACP antibiotic drugs so important right
now?
and thus are a low priority. Governments
and regulators need to find a way to
disease progresses. This will enable
a reasonable price point for a large
We are nearing a tipping point in the incentivise antibiotic development that unmet medical need that we feel
rise of multi-drug resistant bacteria. works for both parties. Other fields, such should be enticing with respect to
Acyl-ACP-dependent products, enzymes, and pathways in bacteria. We can act now to head off this as rare childhood (orphan) diseases, moving a new first-in-class antibiotic
Typical acyl chain lengths are shown in red, while AcpS, the enzyme of interest, is highlighted in blue
looming crisis, or risk returning to a have such mechanisms in place already into the clinic.
pre-antibiotic era where infectious so templates do exist. Hopefully, an
diseases were the top killers, and agreement can be found before multi- What are your plans for future
average human lifespans were less drug resistant bacteria develop into a research and investigation?
the bacterial load for DFI infections,
which would facilitate the healing
Prof McMaster hopes to be one of the than 50 years. crisis. Our antibiotic class works versus
a broad-spectrum, Gram-positive
process. first researchers in over 50 years to When and how did you first start What advantages do you expect the bacteria. We are currently working
being interested in devising new drugs you are currently testing would
develop a new class of antibiotic drugs
on Gram-negative antibiotics, as well
Prof McMaster and his team developed classes of antibiotics? have once they are placed on the as drugs for rare inherited (orphan)
a new class of antibiotics designed to A decade ago I made an intentional market? diseases. In essence, therapies for
eliminate bacteria in DFIs, with an entire tests suggested that the drug has all Prof McMaster hopes to be one of the shift in research focus toward drug We intentionally worked on an antibiotic infectious and inherited diseases.
new structure compared to current the properties required for it to be first researchers in over 50 years to discovery and development. That programme that should have high uptake
antibiotics. This would be the first class successfully used within clinical settings. develop a new class of antibiotic drugs, said, the very first research essay I ever
of antibiotic to target the bacterial in this case specifically designed to wrote – at eight years of age – was on
enzyme holo-acyl carrier protein A CRITICAL PROBLEM tackle diabetes-related foot infections. Alexander Fleming and his discovery of We can act now to head off this
looming crisis [of multi-drug resistant
synthase (AcpS), which is essential for The issue of drug-resistant bacteria is He and his team are also looking to penicillin.
lipid metabolism in bacteria. of great importance, with Dame Sally develop a drug for Gram negative

Prof McMaster tested the new class of


Davies, England’s Chief Medical Officer,
describing it as a “catastrophic threat
infections. What would you say are the biggest
challenges in your field of research
bacteria], or risk returning to a
antibiotics in animal models of DFI, and to the human population.” Developing and how can these be overcome? pre-antibiotic era where infectious
other skin infections, and found them new classes of antibiotic drugs is crucial There is work to be done between
to successfully reduce the bacterial to effectively counteract infections that governments, regulators, and the diseases were the top killers
load in DFIs by over 99%. Further resist currently available treatments.

48 www.researchoutreach.org www.researchoutreach.org 49
Health & Medicine ︱ Dr Gavin Y Oudit

Preventing and
treating complications
of heart failure and
Fabry disease
E
Dr Gavin Y Oudit, a very year, approximately 610,000 develop acute HF and these individuals
distinguished cardiologist people die from heart disease in often continue to suffer from the
from the University of Alberta, the United States, with heart failure condition.
focuses his research on (HF) accounting for one in nine fatalities.
developing ground-breaking Worryingly, according to the American As a result, Dr Oudit and his team
therapies to treat both genetic Heart Association, the number of people are looking to develop novel HF
and non-genetic cardiovascular diagnosed with HF is expected to therapeutic options. Dr Oudit’s
disorders, and to prevent heart increase rapidly in the United States, from studies mainly focus on metabolic
failure. His exciting work into six million to eight million by 2030. Not disorders associated with heart disease,
the role of ACE2 has provided only does this threaten life expectancy neuromuscular dystrophy and Fabry
a fundamental scientific and impact the sufferer’s quality of life, disease – a genetic disorder that can
understanding used in the but the financial implications are also cause cardiovascular complications. causing vasoconstriction (narrowing of the adverse effects of Ang II: examples levels. In fact, Ang 1-7 (a product
development of therapeutic severe. As a result of this increase, the In fact, Dr Oudit’s ground-breaking blood vessels), and increasing blood include ACE inhibitors and Ang II of Ang II degradation) behaves as a
options for cardiovascular, renal total medical costs required to treat the research has already revolutionised the pressure to optimal levels. receptor blockers. These therapeutic cardioprotective peptide, actively
and lung diseases. He has also disease are estimated to rise from $14.3 way clinicians diagnose and treat Fabry approaches have effectively reduced reducing the negative impact of Ang II
provided important insights
billion to $29.2 billion. disease, reducing the risk of sufferers However, Ang II can have an adverse hypertension, improved cardiac by suppressing aldosterone secretion
into various cardiomyopathies
developing HF. Crucially, he has also effect on heart health by causing function and prevented ventricular and inhibiting myocardial fibrosis.
including heart disease
WHAT IS HEART FAILURE? shown that the renin-angiotensin
associated with Fabry disease.
Essentially, HF is a condition whereby
the heart cannot pump sufficient blood
system (RAS) plays a significant role in
HF, and inhibiting its activity can act as
Dr Oudit’s ground-breaking research has revolutionised the
to meet the needs of the body. This can a preventative measure. way clinicians diagnose and treat Fabry disease, thus reducing
be due to a weakening of the muscle
itself, or a deficiency in the volume of THE ROLE OF THE RENIN- the risk of sufferers developing heart failure
blood that fills the heart’s chambers. ANGIOTENSIN SYSTEM (RAS)
Abuse of alcohol, drugs, diabetes and The RAS hormonal system is vital in hypertension, ventricular dilation, remodelling. Although these Excitingly, studies on mice confirmed
obesity can greatly enhance the risk of regulating blood pressure, controlling hypertrophy (thickening of ventricular medications have shown clinical the protective benefits of ACE2 in both
suffering from HF, but genetic defects homeostasis in both the cardiovascular wall) and alterations in chamber promise in patients suffering from HF- HF-rEF and HF-pEF. Clearly, ACE2 could
are also a common contributor. HF can and renal systems. Low blood configuration. These effects result in rEF, they do not protect those afflicted potentially be a revolutionary therapeutic
result from a number of different factors pressure is detected by the kidney, two HF disorders: i) HF with preserved with HF-pEF. tool, although more studies need to
including arrhythmia (irregular heart triggering the release of renin into ejection fraction (HF-pEF), whereby the be conducted to achieve optimal RAS
beat), heart attacks, hypertension and the blood. This enzyme cleaves the left ventricle is stiff, reducing relaxation ACE2 – A NATURAL PREVENTION inhibition and cardioprotection.
cardiomyopathies (disorders affecting plasma protein angiotensinogen to during blood fill before the next AGAINST RAS-INDUCED HF?
the heart muscle). form angiotensin I. Another enzyme, beat, and ii) HF with reduced ejection To address this issue, Dr Oudit and his FABRY DISEASE
ACE (angiotensin converting enzyme) fraction (HF-rEF). This is where the heart team have investigated other strategies Dr Oudit and his colleagues have also
Currently, there is no cure for HF. transforms angiotensin I (Ang I) into cannot pump adequately, expelling less to inhibit the RAS system. The discovery revolutionised the way clinicians treat
However, a combination of simple angiotensin 2 (Ang II) which is a oxygen-rich blood. of ACE2 could provide a solution. and diagnose Fabry disease. This is
lifestyle changes and medication can biologically active octapeptide. Ang ACE2 is a monocarboxypeptidase an X-chromosome-linked recessive
improve quality of life. Nevertheless, II induces the release of the hormone In the past, researchers have attempted that degrades both Ang I and Ang disease that affects around 1,500 to
prognosis can be poor for people who aldosterone from the adrenal gland, to inhibit the RAS system to reduce II, inhibiting the RAS system at two 3,000 people. A mutation in the gene

50 www.researchoutreach.org www.researchoutreach.org 51
Liver Lungs Behind the Bench
Heart Dr Gavin Y Oudit
T: +1 780 407 8569

Research Objectives Collaborators Scientist. He currently directs the Heart


Renin Dr Gavin Oudit’s research focuses on • Maria B. Grant, USA Function Clinic at the Mazankowski
cardiomyopathies and heart failure. He • Bart Vanhaesebroeck, England Alberta Heart Institute.
Angiotensinogen Angiotensin I Angiotensin II and his team have been responsible • Josef M. Penninger, Austria
for ground-breaking work investigating • Peter P. Liu, Canada Contact
Angiotensin preventative measures for heart • Michael West, Canada Gavin Y Oudit MD, PhD, FRCPC
disease and Fabry disease. His research Associate Professor, Department of
converting enzyme (ACE)
is largely focused on elucidating the Bio Medicine, University of Alberta
molecular and cellular underpinnings of Following his academic career at the Clinician-Scientist, Mazankowski
heart failure, but he studies other areas, University of Toronto, Dr Gavin Oudit Alberta Heart Institute
Vasoconstriction and including vascular and kidney diseases, embarked on his training in Internal Canada Research Chair in Heart Failure
increased blood pressure as well. Medicine and the Clinician-Investigator Director of the Heart Function Clinic
Program of the Royal College of Division of Cardiology, 2C2 Walter
Kidney Funding Physicians and Surgeons of Canada. Mackenzie Health Sciences Centre
Funding support was provided by the Following this, he completed a post- Edmonton, Alberta, T6G 2B7
Canadian Institutes of Health Research doctoral fellowship in the molecular Canada
(CIHR), Alberta Innovates-Health biology of heart failure before joining
Solutions (AI-HS), Heart and Stroke the University of Alberta, where
Foundation (HSF), and the University of he currently works as an Associate
Alberta Hospital Foundation. Professor, Cardiologist and Clinician-
encoding α-galactosidase A (a hydrolase Diagnosis of Fabry disease is very
difficult, and many individuals are not
enzyme involved in fat metabolism)
confers insufficient degradation of
glycosphingolipids, resulting in the
accumulation of fatty deposits in cell
diagnosed until later in life – Dr Oudit
storage organelles called lysozymes. and his team aim to change this
Cell function is impaired, causing

Q&A
damage to a variety of tissues, including diagnostic tool called T1 mapping. The for Fabry disease in patients
the kidneys, skin, eyes and heart. term ‘T1’ refers to the ‘relaxation time’ of with undiagnosed hypertrophic of the ACE2 gene. These differences gadolinium contrast. It may serve
HF is the primary cause of death for the cardiac muscle. Interestingly, in Fabry cardiomyopathy and patients with chest may relate to sex-based differences as an important imaging biomarker
individuals afflicted with Fabry disease, disease this T1 time is shortened, which pain syndrome with normal epicardial How does angiotensin II specifically in cardiovascular disease with women to track the progression of Fabry
so early diagnosis is essential to prevent is a rare phenomenon. T1 mapping is coronary arteries. The detection of new cause heart failure? having a better prognosis compared to cardiomyopathy.
severe heart damage. an MRI technique, but is significantly cases of Fabry disease is essential since Angiotensin II is a peptide hormone men.
more powerful than ultrasound or the use of enzyme replacement therapy which is produced in the circulation Are you researching any other ways
Unfortunately, symptoms of Fabry regular MRI, as it can detect microscopic has important beneficial effects. and in the heart tissue. It produces high How long will it take for ACE2 to to prevent heart failure?
disease are subtle and are often changes in the heart and determine blood pressure and causes progressive be used commercially to treat heart Yes, we are developing novel apelin
associated with other more common damage severity early on. As a result, Overall, the work of Dr Oudit and his myocardial and renal damage leading failure? analogues as potential therapies for
disorders. Examples of these symptoms patients suffering from chest pain and colleagues is making an outstanding to heart failure. Between three and five years. heart failure and we are screening for
include hearing difficulties, kidney hypertrophic cardiomyopathy can contribution to the field of cardiology. cardiomyopathies including Fabry
problems, fatigue, eye abnormalities be screened for Fabry disease, and, By developing novel diagnostic tools and ACE2 is an X-linked gene – can How does T1 mapping detect early disease.
and heart defects. Therefore, diagnosis if detected, can undergo Enzyme therapies to treat heart failure, the team genetic mutations enhance the risk heart damage in Fabry disease
is very difficult, and many individuals are Replacement Therapy. This effective are drastically improving the quality of of developing heart failure, and if so, patients?
not diagnosed until later in life – Dr Oudit treatment uses an enzyme called life of many people all over the world. how can this be prevented? T1 mapping is a very sensitive and
and his team aim to change this. agalsidase beta to degrade the fatty Yes, ACE2 is X-linked so women have specific marker of Fabry cardiomyopathy
deposits in the cells. two copies and men have one copy and can be used without given
T1 MAPPING
He and his team at the University of SCREENING FOR FABRY DISEASE
Alberta have developed an innovative Dr Oudit’s team is currently screening

52 www.researchoutreach.org www.researchoutreach.org 53
Health & Medicine ︱ Dr John LaCava
expression and commonly implicated in CDI’s antibodies Interactome screening
against endogenous Cryomilled
cancer progression. Changes in these transcription factors

Raising antibodies against


patient tissues
proteins are often responsible for the
unregulated proliferation of tumours, 100

95
90
716.2

so understanding their associations and


85
603.2
80

75

70 943.4
65
815.2
60
1257.4
55

Relative Abundance
390.1

activities in both the natural and disease


1100.2 1427.4
50
1612.4
45

protein complexes
40
35 1213.2 1258.3

Protein Complexes /working conditions


30
1054.3
25 489.1
1195.3
926.4 1409.4

states will assist with identifying potential


20 1444.6
745.1 1408.6
604.2
15
541.0 854.8 1001.4
10
373.0 691.3 1560.3 1652.3
5 392.7
1481.1

400 600 800 1000 1200 1400 1600


m/z

targets for therapy. Quantitative characterisation of IP


performance by mass spectrometry

NOTHING WORTHWHILE IS EVER


EASY: DISCOVER, OPTIMISE,
REPEAT

P
Cryomilled human Endogenous-Complex-IP-Competent
This task is made more challenging cell lines antibody to market Interactome
curated
Dr John LaCava of The roteins are vital for the inner living cells to access their contents, thus because of the now widely recognised
Rockefeller University has workings of cells. Complex releasing a complex mixture of proteins, problem that many antibodies are not
FIGURE 1. One implementation of the modular pipeline: The parameters of antibody performance are
identified a gap in the current networks of interactions form then uses antibodies to attach to a capable of reliably capturing their target assayed via screening in model cell lines as well as clinical samples. The underlying process is described
availability of target-specific between protein molecules, and specific target protein, thereby capturing protein and its associated interaction in greater detail in Hakhverdyan et al. Nature Methods (2015). Well-performing antibodies characterised
antibodies for the analysis of because these associations drive it and permitting it to be pulled away partners. Moreover, even otherwise in this way can be relied upon to effectively immunoprecipitate (IP) endogenous protein complexes
when the discovered experimental parameters are employed. Curated, disease-related interactions
intracellular protein-protein cellular activity, an accurate knowledge from the mixture. Importantly, the reliable antibodies may not perform and the antibodies targeting them may also be of diagnostic and/or therapeutic value – identifying,
interactions. Using the latest of them is vital for understanding cell antibody must be able to bind to its well under all experimental conditions, differentiating, and modulating disease states. The data contribute to a global human interactome map.
antibody production techniques, biology and biochemistry. One way target in the context of the physical and protein associations existing in

It is thought that as little as 10%


alongside immunoprecipitation of gaining an insight into the protein associations the target forms with other cells are not all equally stable and
and mass spectrometry, he aims interaction networks forming within a proteins in the cell, and with minimum analytically tractable once they are
to identify important interactions
between transcription factors
specific cellular population is through
immunoprecipitation – using the
off-target binding. When done properly,
immunoprecipitation permits groups of
released from cells and subjected to
immunoprecipitation. Therefore, each
of human protein interactions are
and other macromolecules which
are implicated in disease.
molecules of the immune system to bind interacting proteins to be collectively antibody and immunoprecipitation currently mapped
proteins and draw them out of solution so purified from cells. Co-purifying proteins experiment must be subjected to
they can be studied. are said to be guilty by association. procedural optimisations, a labour- processes linked to the target of the resected patient tumours – exploring
That is, if the biological function of one intensive and often time-consuming immunoprecipitation (false positives). compositional differences specific to
GUILT BY ASSOCIATION or more of the proteins in the purified process. Dr LaCava and his collaborators Hence, different components of cancerous states.
Immunoprecipitation is a molecular group is known, the rest often also prove at CDI have therefore set about the interactome require different
technique capable of providing an to be implicated in the same or related generating and evaluating a suite of parameters to be in place during A NEW TOOLBOX FOR BIOMEDICAL
accurate picture of protein associations. biological functions. With antibodies new antibody candidates, as well as immunoprecipitation for the experiment RESEARCHERS
The technique involves breaking open against every human protein, researchers developing robust processes to use to be robust and results physiologically Using the building blocks of their
could map the vast networks of protein them in optimal conditions. accurate. To overcome this, Dr LaCava screening techniques, specific
associations responsible for life. When and his colleagues at the National Centre antibodies, and identified optimum
protein associations go wrong, the The process is not entirely for Dynamic Interactome Research conditions, the team hope to be able
resulting altered interactions may lead straightforward. Protein interactions (NCDIR) developed a high-throughput to capture a range of complexes for the
to disease. The study of these changes within cells (in vivo) exist in a highly screening method using mass next stage of the programme.
therefore has high clinical value. specific set of naturally occurring spectrometry based proteomic analyses,
environmental parameters. These allowing precise in vitro conditions Presently, antibodies are typically
A CENSUS OF PROTEIN conditions are inevitably altered during to be performance classified. Their generated on a case-by-case basis.
ASSOCIATIONS immunoprecipitation, which requires results reveal the optimal conditions for In such a workflow, a protein of
Dr LaCava’s work is important because, the cells’ contents be transferred into immunoprecipitation. interest (such as a recombinant human
despite significant advances in artificial conditions within test tubes transcription factor) is, for example,
genome characterisation and protein (in vitro) in order to mix them with Armed with these techniques, the injected into a mouse, provoking an
identification, the global networks antibodies used for protein capture. An team are now focusing their efforts immune response. Antibody producing
of protein interactions that occur within undesirable yet common side-effect of on evaluating commercially-available B-cells are then harvested from the
cells (dubbed interactomes) remain transferring proteins out of cells into an antibodies that target human mice and cultured in the lab to provide
poorly characterised. It is estimated that artificial environment is that interacting transcription factors, which have been a renewable source of those antibodies.
10% of human protein interactions, or groups of proteins sensitive to the produced under the National Institute of In the hands of Dr LaCava and CDI,
fewer, are currently mapped – and this change will rapidly dissociate from one Health’s (NIH) Protein Capture Reagents these antibodies are tested for their
figure does not include the disease- another – preventing their co-capture Program (PCRP). Their immediate aim efficacy in immunoprecipitation, as
specific interactions which are arguably during immunoprecipitation. These is to characterise these antibodies for described above. CDI has made a
of most interest. As part of their protein associations therefore remain their ability to immunoprecipitate protein major advance in the field developing
collaboration with CDI Laboratories invisible to detection (false negatives). complexes formed with transcription a proprietary monoclonal antibody
Inc., Dr LaCava’s group is currently Similarly, when bona fide interactions factors within established cell lines. production pipeline, named Fast-
focused on identifying interactions dissociate, spurious interactions Ultimately, the team plans to use the MAb®. Overall, however, this remains an
involving transcription factors, proteins may form, wrongly implicating these same techniques to purify transcription expensive, labour-intensive and time-
which are master regulators of gene spurious interactions in biological factor protein complexes directly from consuming process.

54 www.researchoutreach.org www.researchoutreach.org 55
What if this process could be sped up?
In order to meet the ultimate goal of
mapping the entire human interactome
in health and disease, good antibodies
the field. Another major benefit of this
approach is that the resulting antibodies
target endogenous protein forms.
largest-content, full-length human
protein microarray in existence (able
to screen antibodies against nearly Behind the Bench
against every human protein and
variant are needed. To solve this
Dr LaCava’s approach is providing novel Dr John LaCava
problem, Dr LaCava and CDI have solutions to long-standing, under-articulated E: jlacava@rockefeller.edu T: +1 212 327 8136
taken to injecting immunoprecipitated W: http://www.b13logy.com CDI Laboratories Inc. http://www.cdi-lab.com/
protein complexes, containing problems in protein biochemistry and National Center for Dynamic Interactome Research http://www.ncdir.org/

affinity proteomic research


collections of physically and functionally
linked proteins, into mice. In doing so,
they simultaneously raise antibodies Research Objectives Bio Contact
against numerous proteins present This alleviates the need to genetically twenty-thousand human proteins), Dr Dr LaCava specialises in macromolecular Dr LaCava is a research faculty member at John LaCava, PhD
interactions analyses. Working in The Rockefeller University and the New York Laboratory of Cellular and Structural
in the mixture; these antibodies are modify cells, appending affinity tags to LaCava’s team is determined to further
collaboration with CDI Laboratories, he University School of Medicine, Institute for Biology
then validated in immunoprecipitation target proteins in order to purify protein expand the current possibilities of and his research team are developing Systems Genetics. He is a senior researcher The Rockefeller University
as above, and used to mine the complexes using an antibody against immunoprecipitation techniques and monoclonal antibodies capable of binding at the NIH’s National Center for Dynamic 1230 York Avenue
interactome for new protein the tag. Affinity tagging is currently bring this to the commercial marketplace to constituents of protein complexes found Interactome Research, serves as an R&D New York, NY 10065
associations – generating a virtuous used in most interactome studies due themselves. in established and clinic-derived cancer collaborator and scientific advisor for CDI USA
cycle. Dr LaCava hopes to exponentially to the sparsity of native antibodies cells. Laboratories Inc., and has recently co-
expand the portfolio of antibodies available. However, this method is only The ultimate goal is of course to improve founded B13LOGY LLC.
Collaborators
useful for interactome studies and, widely applicable in model cell lines that patient outcomes and develop new
• National Centre for Dynamic Interactome Funding
likewise, rapidly increase the coverage can be easily genetically manipulated drugs capable of combatting cancer. Research (NCDIR) National Institutes of Health (NIH)
of bona fide human protein-protein on a genome-wide scale, leaving more Indeed, the team believe that the intact, • CDI Laboratories Inc. (CDI)
associations. disease relevant clinical samples off the purified protein complexes they obtain

Q&A
This approach also has added value. table. will provide an unparalleled opportunity
immunoprecipitation technology diseased protein complexes to more
When using intact, endogenously to test drug candidates for their ability
for protein-target discovery and greatly resemble and/or propagate the
assembled protein complexes as Taken together, the drive for this research to modulate proteins as they are found
characterisation. The research-use only healthy state. A prominent example of
immunogens, some of the antibodies is to provide tools for expanding within cells, and in doing so, treat disease. What are the advantages and antibody market generates between $2.2 the promise (and challenges) of anti-
generated may recognise variables biomedical research capabilities Hence, the benefits of this research disadvantages of the high-throughput billion and $2.7 billion per year and growing tumorigenic treatments resulting from
that are part of the gamut of naturally and findings while also improving are likely likely to be recognised across screening approach? (2015).1,2 ‘drugging’ protein-protein interactions is
occurring protein processing. These reproducibility. both diagnostics and therapeutics, as it Advantages: Our approach speeds up Our market research indicates that the embodied by the development of nutlin,
may include alternative isoforms becomes increasingly possible to quickly the discovery of conditions for successful proteomics global economy is projected to the first small-molecule inhibitor of the
immunoprecipitation and identifies be valued at over 20 Billion USD by 2021. p53–MDM2 interaction3 – illustrating
and truncations, post-translational UNIQUE APPROACH TO AN OLD characterise the biochemical profiles of
multiple successful working conditions that, if we thoroughly mine disease-
modifications, and interfaces formed PROBLEM tumours and develop weapons against that typically reveal novel interactors of What makes you think that this linked protein networks, diagnostic and
only when proteins are associated Dr LaCava’s approach is therefore their aberrant activity. the protein of interest. This approach technique will succeed where others therapeutic strategies will emerge. We
together (referred to as the quaternary providing novel solutions to long- allows us to study how the signal and have failed? aim to be among the vanguard of this
structure). Creating reagents that standing, under-articulated problems noise of the immunoprecipitation Firstly, others have not had the ability global effort.
can distinguish bound and unbound in protein biochemistry and affinity experiment change across many to screen antibodies for success
proteins, and capture only those proteomic research. Leveraging CDI’s experimental parameters, revealing in immunoprecipitation in such a What is the most challenging aspect of
how in vitro conditions affect protein comprehensive way. Secondly, others have this work?
protein complexes in a given state of proprietary monoclonal antibody
behaviours in complexes. Such lacked the array-based pre-screen of CDI to There are so many challenging aspects
protein associations is a ‘holy grail’ of production pipeline, which uses the knowledge has clear basic research and select for antibodies likely to be specific to of the work – but among the most
industrial applications. begin with. Finally, to our knowledge, others challenging is assessing which proteins
Disadvantages: The technique does have not been able to readily purify enough among those purified are true positives
require training to master. It requires endogenous complexes from human cells and which are false positives. While there
special equipment and screening to routinely inject them in mice for antibody are many potential indicators, and large
FIGURE 2. Another anti-tag antibody Interactome screening Scale-up / inject in mice Generate consumes a lot of material. Although, production – a recent preparative ‘trick’, amounts of public data to draw from,
implementation of the antibodies / the material use is efficient on a “per coupled with our already highly effective there’s no foolproof method to score
modular pipeline: Affinity HuProt screen
discovery” basis, since we find valuable, protocols helped us make the leap. an interaction accurately without deep
tagged human protein
complexes can be optimised CDI’s
otherwise invisible interactions when we knowledge of the underlying biology.
and scaled up for injection Fast-MAb® look through the lens provided by the How will this research impact on cancer Analysis is a bottleneck, which B13LOGY
into mice to generate screen. diagnosis and therapy? LLC is hoping to address.
numerous monoclonal
Protein Complexes /working conditions
When aberrant molecular interactions are
antibodies against physically How big is the market for these sorts identified, they may prove to be diagnostic References:
and functionally related
of biochemical tools? of cancer sub-types (or prognostic of 1. Fung P. A. BioCompare Antibody
proteins, as present in
vivo. These reagents are The global antibody market is in excess of outcomes), and rational approaches to Market Report. (2015).
then forwarded to the $80 billion and continues to expand each intervene may be effectively employed as 2. Baker M. Antibody anarchy: A call to
Figure 1 pipeline. The year. The antibody market comprises therapies. A therapeutic approach may order. Nature. (2015).
data contribute to a global three major sectors: therapeutic seek to reverse the aberration by e.g. 3. Khoo et al. Nature Reviews Drug
human interactome map. For Cryomilled human cell lines applications, diagnostic tests and stabilising a labile diseased interaction, Discovery. (2014).
more details about HuProt ectopically expressing affinity-
tagged protein complexes research-use. or by destabilising a stable diseased
screening see http://cdi-lab.
com/HuProt_proteome_ Interactome curated Interactome screen & characterise new antibodies Scientific research institutes use interaction, or otherwise modulate
(Figure 1)
microarray.html

56 www.researchoutreach.org www.researchoutreach.org 57
Health & Medicine ︱ Dr Margot Taylor

Impaired theory of mind


associated with very preterm
birth – an invisible handicap
E
Dr Margot Taylor, Director of verybody has a unique set of beliefs ToM IN VERY PRETERM-BORN
Functional Neuroimaging at and principles, and the ability to CHILDREN
the Hospital for Sick Children appreciate these differing opinions Research has shown that poor ToM
and Professor at the University is an essential part of social living. This also occurs in very preterm (VPT) born
of Toronto, is investigating phenomenon is known as ‘Theory of Mind’ children: babies born at a gestational
how very preterm (VPT) birth (ToM) – termed a ‘theory’ because the age of less than 32/40 weeks. In Canada
impacts social cognitive function mind cannot be directly observed. We can alone, over 4000 VPT babies are born
including Theory of Mind only interpret what others are thinking/ every year. Even though improvements in
(ToM), a skill that enables us to feeling by their speech, body language neonatal intensive care mean that fewer
appreciate that perspectives and and facial expressions. These cues allow us VPT infants suffer from serious health
beliefs of others can differ from to visualise that person’s perspective and conditions, over half of VPT children
our own. By using neuroimaging anticipate their behaviour. experience difficulties such as academic
techniques, Dr Taylor has underachievement and cognitive
explored the neural networks As children develop, their ability to impairment, including ToM deficiency.
that underpin the association comprehend these emotive indicators
between VPT birth and ToM.
improves alongside their emotional Despite the prevalence of VPT births
intelligence. ToM ability typically and the subsequent detrimental
emerges between four and five years lifelong impact, little is known about
of age and development continues how neural pathways are affected
through adolescence into adulthood. by early birth, which leads to poor
In some cases, however, children do not
master ToM and struggle to understand
social-cognitive abilities, including
poor ToM skills. By using innovative
either switches the location of the ball
or drops it into the same hat. During the
Using innovative neuroimaging
perspectives different from their own. neuroimaging techniques, such as second image in the pair, Jill is either techniques, Dr Margot Taylor and her
colleagues have been the first team to
As a consequence, these children may magnetoencephalography, coupled present for the ball switching or absent.
have difficulties across a range of social with classic ‘false belief tests’, Dr Margot Therefore, if Jill does not witness the
skills, such as understanding what others
mean during daily social interactions or
Taylor and her colleagues, Sarah Mossad
in particular, have been the first to
ball being switched, she has the false
belief that the ball is still located in investigate the impact of very preterm
having empathy for others. investigate the impact of VPT birth on
this critical social-cognitive skill.
the original hat. Having seen the two
cartoon images, participants were then
birth on social cognitive development
Individuals who suffer from autism asked the question: ‘Where does Jill
spectrum disorder, attention deficit FALSE BELIEF TASKS think the ball is?’ and responded using to compare neural activation associated children. Both groups engaged some
disorder and schizophrenia are A standard protocol used to assess a button box. 300 trials with both true with ToM and false belief in both VPT of the regions involved in false belief
particularly prone to deficient ToM. ToM ability is the ‘false belief task’, and false belief examples were run. and FT children. MEG measures brain processing, referred to as the ToM
As a result, these children and adults whereby a person must realise that Results showed no significant difference activity by recording magnetic fields or ‘mentalising’ network. In a previous
often find social situations stressful and another individual holds a belief about in behavioural performance. When produced by electrical currents, using study, performed on adults, Dr Taylor
difficult to cope with. However, because a situation that is different from their tested outside the scanner on various sensitive magnetometers. This innovative highlighted this network using MEG.
deficits in ToM are only apparent in own and from reality. The ‘Jack and scenarios requiring ToM skills, however, technique can provide millisecond Activation begins in the occipital regions,
social situations, ToM impairment is Jill’ false belief task was used by Dr VPT children performed significantly temporal information along with near- followed by the right inferior frontal
often not recognised until children Taylor and her team to compare ToM worse than FT children. millimetre spatial resolution, giving a gyrus and the temporal-parietal junction.
start school, where adaptive social abilities in VPT vs. full term (FT) children. highly-detailed map of the brain’s activity.
functioning becomes crucial, not only Participants saw a series of cartoon MAGNETOENCEPHALOGRAPHY Results showed that activation in all
to making friends and dealing with new images projected in sequential pairs on During this task, Dr Taylor and her Despite similar behavioural performance regions was reduced and often delayed
and complex social situations but also a screen. In the first image, Jill sees Jack colleagues used the state-of-the-art in the false belief task in MEG, Dr in the VPT compared to the FT group.
in learning. about to drop a ball into either a blue brain imaging technology known as Taylor showed that neural processing Key findings indicate the importance of
or red hat. In the second image, Jack magnetoencephalography (MEG), is different in VPT compared to FT the temporal-parietal junction in ToM

58 www.researchoutreach.org www.researchoutreach.org 59
Behind the Bench
Network of brain regions involved
in Theory of Mind (ToM) processing
in typically developing children and
adults. This network includes the right
temporal parietal junction (large green

Dr Margot J. Taylor
sphere), which is a region known to be
crucially involved in ToM processing.
Compared to their full-term peers,
children born very preterm,
show reduced and delayed
recruitment of these E: margot.taylor@sickkids.ca T: +1 416 813 6321
regions during W: http://www.sickkids.ca/Research/margot-taylor-lab/Index.html
ToM tasks.

Research Objectives G. Sled, Dr Charline Urbain, Dr Hilary E. Contact


Dr Taylor’s research utilises innovative Whyte, Dr Mary Lou Smith, Dr Elizabeth Dr Margot J. Taylor
brain imaging technology, such as Pang and Sarah Mossad Diagnostic Imaging
magnetoencephalography (MEG), The Hospital for Sick Children
functional magnetic resonance imaging Bio 555 University Avenue
(fMRI), and MRI to understand the Dr Taylor received her doctorate Toronto, Ontario
neural bases of cognitive development. from McGill University in 1981 and M5G 1X8
came to SickKids in Neurology as Canada
Funding Director of Evoked Potential Labs. She
• Canadian Institutes of Health moved to Toulouse, France in 1998 as
Research (CIHR) Directeur de Recherche, CNRS before
being recruited back to SickKids in
Collaborators 2004, as the Director of Functional
Dr Evdokia Anagnostou, Dr Benjamin Neuroimaging.
T. Dunkley, Dr Jason P. Lerch, Dr John

Q&A processing is occurring. The speed of


thoughts and where they are happening
VPT children show amazing resiliency
despite early brain injury; we want to
Why is Theory of Mind (ToM) so can change enormously with age and understand what underlies that, to be
and false belief processing. Following
the inhibition of one’s own beliefs,
Social-cognitive dysfunction is a common important?
Theory of Mind (ToM) allows us to
with clinical populations; being able to
identify what the differences are allows us
able to foster it in all of these high-risk
children.
in order to see from another person’s sequelae of VPT birth and disturbances understand the beliefs, emotions or to understand why some groups are not
perspective, the temporal-parietal mental states of others and that they able to master ToM skills adequately. How can we treat impaired ToM?
junction is activated. MEG imaging in developing these skills have profound can be different from our own; this There are interventions (often

long-term consequences academically


showed that FT children recruit the right allows us to predict and understand What are the main neurological developed for children with autism)
angular gyrus, temporal-parietal junction others’ behaviour and is thus critical to differences between very preterm and that can teach children how to
(rTPJ) more than VPT children in false
belief. In contrast, the VPT children
and socially adaptive social interactions. full-term infants?
VPT infants have a much higher risk of
behave more appropriately in social
circumstances, and better understand
recruited primarily temporal brain Why is impaired ToM prevalent in brain injury, and can sustain white matter what others mean with language and
regions to successfully complete the underlying ToM in VPT and FT children. social situations and forge relationships. very preterm born children? injury at birth. These effects can be expressions. The children also need
task, suggesting their use of alternative She and her colleagues are continuing In children, this in turn would impact We believe that very preterm birth seen throughout childhood, but do not to learn what impact some of their
strategies and underutilisation of the their investigations into the cognitive their academic performance. Therefore, impacts the development of brain relate directly to the social and cognitive own behaviours have on others. These
mentalising network, which may explain consequences of VPT birth. They it is essential that we develop methods networks critical for social-cognitive deficits that this group often experiences. interventions are usually based on
impairments in ToM ability frequently propose a series of longitudinal studies to identify ToM impairment early abilities; our studies will determine the The deficits are due to atypical brain intensive social modelling and role-
observed in VPT children. that focus on investigating how neural on. Dr Taylor’s team aim to establish atypical brain function underlying this. function and that needs to be studied by playing approaches.
patterns change as both VPT and FT predictive models that will identify techniques such as MEG. Some of these
FUTURE RESEARCH children develop, using cognitive and children who are more vulnerable to What are the benefits of using
The brain is an extremely complex organ social-cognitive tasks. developing social-cognitive difficulties. magnetoencephalography Theory of Mind (ToM) allows us to
to examine neural networks
understand the beliefs, emotions or
and a full understanding of the neural Targeted intervention techniques could
underpinnings of social cognition – both The impacts of impaired social cognition then be used to teach these children underpinning ToM?
good and poor abilities – is difficult to
achieve. However, Dr Taylor’s ground-
can be very detrimental and a lifelong
handicap. Without effective intervention,
ToM skills and help them to develop
their social-cognitive abilities, greatly
MEG is an exceptional neuroimaging
technique as it provides information
mental states of others and that they
breaking research has highlighted individuals may have a reduced quality improving their quality of life. on both where and when in the brain can be different from our own
some of the key neural differences of life, as they struggle to navigate

60 www.researchoutreach.org www.researchoutreach.org 61
Earth and Environment ︱ Professor Shanaka (Shan) de Silva
The potential impacts make

Supervolcano Forensics:
Pyroclastic flows from Sinabung volcano on the
understanding supervolcanoes a task of 2nd August, 2017. Sinabung lies just 20 miles to
the utmost importance, and one that is the north of Toba and shares geochemical and
age characteristics with Toba.
being tackled by Professor Shanaka de Credit: Shanaka de Silva
Silva and his colleagues at the College
of Earth, Ocean, and Atmospheric
Sciences, Oregon State University. In
unravelling the mysteries of the Earth’s biggest natural catastrophe particular, the group are addressing a
number of questions:

N
1. Magma bodies that feed
ext to asteroid impacts, supervolcanoes are the most supereruptions are likely at least an
To many, if not most, the word ‘forensics’ invokes
catastrophic natural hazard on Earth. On average, order of magnitude larger than the
images of the very small – DNA, fingerprints, etc., – but
supereruptions have occurred on Earth approximately calderas they form and develop over
for Professor Shanaka de Silva and his colleagues
every 100,000 years, blanketing surrounding regions with hundreds of thousands to millions of
at the College of Earth, Ocean, and Atmospheric
Sciences, Oregon State University, ‘forensics’ is being thousands of cubic kilometers of volcanic material and years. Questions remain as to how
used to investigate something altogether bigger. The affecting the global climate. During these eruptions, collapse such large volumes of magma can
team is using a multidisciplinary approach to reveal the of the magma chamber roof leaves a caldera (a crater tens accumulate in the crust and eventually
secrets of ‘supervolcanoes’ and supereruptions, calling of kilometers in diameter). In the following decimillennia, the erupt, rather than cool and solidify into
on expertise in the fields of geophysics, geochronology, volcano recovers as magma readjusts to the disturbance (rather a granite.
petrology, geochemistry, and numerical modelling. like the surface of water when something is dropped into it) 2. The very conditions that promote zircon) to date volcanic processes. work has confirmed the presence of
causing the ground above to swell (‘uplift’) and deform – a the growth of large magma bodies This work has focused on calderas large low velocity zones (i.e., partially
process known as resurgence. Earthquakes, lake tsunamis and demote the likelihood of eruptions. in the Central Andes and has shown molten areas) that extend hundreds
fresh eruptions characterise this recovery, posing significant and Why then do these magma systems that: (a) crystals can form in the of kilometres across and tens of
continuing hazards. eventually fail and erupt? storage region several 100,000 years kilometres deep.
3. After catastrophic supereruptions, before eruption; and (b) most magma 4. N
 umerical modelling (led by
the system recovers during the in the storage region actually remains collaborator Patricia Gregg), that
‘resurgence’ and ‘restlessness’ stages non-erupted. uses mathematical models to predict
(or as Professor de Silva describes it, 2. Geochemistry and petrology how systems will behave under given
‘the afterparty after the big dance’). (including work by graduate students conditions. This work has shown
Why does this happen and what are Dale Burns, Stephanie Grocke, Chris that: (a) the rheology (whether brittle
the driving mechanics and time scales? Folkes and collaborator Jan Lindsay), or ductile) of surrounding rock is
Since all currently active calderas which uses the chemistry and textures a controlling factor; (b) negative
(e.g., Yellowstone, Campi Flegrei, of both liquid magma and magmatic feedbacks between magmas’ thermal
Long Valley, Toba) are resurgent and minerals to understand magma history energy, rock plasticity, internal
restless, how long will this last and (e.g., storage depths, temperature, pressurisation and likelihood of
what is the hazard posed? water content, interaction with other eruption promotes growth rather
4. Since many large calderas erupt magma, speed of ascent). The team than eruption; (c) eventual failure of
repeatedly, going through cycles of has confirmed (a) the multi-stage large magma chambers (i.e., eruption
eruption and recovery, what is the evolution of magma chambers, onset) is a function of roof rheology
relationship between supereruptions with distinct changes in volume, and geometry; once reservoir volumes
and resurgence? composition, and heterogeneity; reach 104–105 km3, the crust is
and (b) that thermally and chemically unable to support them and the roof
PIECES OF THE PUZZLE homogenous magmas reside in the collapses, producing calderas of up to
Professor de Silva and his colleagues are storage region both before and after 103–104 km2, consistent with the largest
gathering information using different a supereruption, and drive resurgent calderas on Earth.
scientific techniques – an approach they activity. These magmas do not solidify
have termed Supervolcano Forensics – owing to regular periodic injections of The work of Professor de Silva’s
at calderas around the world. Students fresh, hot magma from depth. group, grounded firmly in field-based
and postdoctoral researchers have 3. Geophysics (led by collaborators observation of the deposits and
conducted much of this ground- from the PLUTONS project), including stratigraphy (the relative temporal and
breaking work, examples of which the use of seismic waves (i.e., waves spatial relation of events) is showing
include: produced by earthquakes and magma that supervolcanoes are surface
1. Geochronology (led by graduate movement) to generate 3D images manifestations of crustal scale magmatic
students Casey Tierney, Chris Folkes, of the crust below calderas. This activity. The development and longevity
Jamie Kern, Jason Kaiser, Rodrigo
Iriarte and collaborators Axel Schmitt
and Martin Danišík), which uses
Next to asteroid impacts, supereruptions
The Earth’s largest volcanic lake, Toba (Sumatra, Indonesia) fills the 100 kilometres long and 30 kilometres wide Toba caldera that formed 74 ka in the Earth’s
the decay of radioactive isotopes
in magmatic minerals (i.e., crystals
are the most catastrophic natural hazard
on Earth
largest recent supereruption. Samosir Island, in the center, is the caldera floor that was uplifted almost a kilometer during post-superuption resurgence.
GeoCover Landsat 7 satellite image in infrared and visible light courtesy of NASA. within the magma; for example,

62 www.researchoutreach.org www.researchoutreach.org 63
Behind the Bench
The life cycle of a supervolcano like Toba
caldera. Top – As magma accumulates the crust
of the earth is upwarped and stretched. Faults
propagate from the surface downwards. Magma
is kept hot by continued intrusion from deep
(red) (105 to 106 years). Middle – Supereruption
- Eventually the faults intersect the magma and
eruption initiates as the roof blocks collapse
into the magma chamber acting like a plunger
to force the vesiculating magma out as ash, gas,
Professor Shanaka (Shan) de Silva
and pumice at supersonic speed (days to weeks).
Bottom – Resurgence. The caldera may fill with E: desilvas@geo.oregonstate.edu T: +1 541-737-1212 W: http://ceoas.oregonstate.edu/
water. The magma system and crust readjust
uplifting the collapsed roof blocks and leaking
small eruptions through the collapse faults (104
to 105 years) College of Earth, Ocean, and Atmospheric Collaborators Research Objectives
Sciences • Patricia Gregg, University of Illinois Professor Shanaka de Silva and his many
104 CEOAS Administration Building • A xel Schmitt, University of Heidelberg, collaborators are currently investigating the
Oregon State University, Corvallis Germany most devastating natural events on Earth,
OR 97331-5503 USA • Martin Danišík, Curtin University, Australia supereruptions. With this project, Prof de
• Ray Cas, Monash University, Australia Silva and his team are working to gain a clear
Bio • Jan Lindsay, University of Auckland, New understanding of the processes and timescales of
Shanaka de Silva is a Professor of Geology and Zealand these supervolcanoes as this is vital for our ability
Geophysics at Oregon State University. With •G
 raduate Students: Adonara Mucek, Stephanie to address potential hazards in the future.
of supervolcano magmatic systems
fieldwork as a point of departure, Shan, students, Grocke, Jason Kaiser, Dale Burns, Rodrigo
depend on the interplay between heat
and collaborators have adopted a “forensics” Iriarte, Jamie Kern, Katharine Solada, Chris Funding
transfer and the mechanical strength
approach to understanding supereruptions and Folkes, Jade Bowers National Science Foundation (NSF), Geological
of the crust. Without this feedback,
supervolcanoes in the Central Andes, Japan, • PLUTONS Team (various collaborators) http:// Society of America Research Grants Program
magma could not be stored in large
China, Sumatra, New Zealand and the Italian Alps. plutons.science.oregonstate.edu
volumes; it would erupt in small events,
or solidify too early. This in turn controls
the eventual size of the eruptions and
calderas.

As an integrative framework and with an


Q&A
Where (and when) will be the next
flows. Beyond this, depending on the prevailing
winds there could be continent scale impacts
on transportation, power infrastructure, water
What new technologies and/or scientific
advances will help us to better understand
supervolcanoes?
eye to hazard assessment, Professor de supereruption? resources, and agriculture. Communication We are still in infancy when it comes
Silva and his colleagues are developing The most likely place for a future supereruption will almost certainly be limited and air traffic to understanding volcanoes, not just
a simple model that frames calderas is a location where there has been such an limited due to airport inoperation. Global supervolcanoes. Critical to understanding this
behaviour as a reaction to changes in the eruption in the past. We know that large impacts are debated, but it is commonly thought is what is happening in the magma systems.
balance of forces in the crust and magma calderas like Toba and Yellowstone have that significant cooling (due to atmospheric While we are beginning to understand some of
system. In this model, the caldera had multiple eruptions in essentially the aerosols) for many years that will adversely the signals volcanoes broadcast, the problem
cycle is a continuous loop. An exciting same location. If the factors that led to their impact agriculture, the food chain, and human with supervolcanoes is that they operate on
possibility is that since the temporal and formation and evolution remain the same activities is the most likely global impact. Given much longer time scales than normal volcanoes
spatial scales of deformation associated (largely controlled by plate tectonics), these the interconnectedness of the global economy, a and over much larger spatial scales. This is
with pre-eruptive development of large Professor de Silva and his colleagues are calderas are the most likely location. supereruption in any part of the globe is likely to a huge challenge, but advances are being

gathering information using different


magma systems is quite different from be a global “Black Swan” event. made on several fronts from understanding
those associated with restlessness, Current statistics suggest that the Earth how magma systems are built and evolve,
the transition from resurgence and
restlessness to pre-eruption build-
scientific techniques – an approach they experiences a supereruption (Magnitude, M 8)
approximately every 100,000 years. However,
What is the radius of total destruction for a
supereruption?
the time scales over which these systems
develop, the rates and time scales of magmatic
up could, in principle, be detected. have termed Supervolcano Forensics there have been at least two such eruptions in About 100 km is a generally agreed value. processes, and what leads to eruption versus
Part of the challenge is nailing down the last 74 ka, and it is likely that our inventory How far away could you be from a supereruption storage. While we are improving our ability
the temporal and spatial scales of of Earth’s supereruptions is incomplete. and still hear it? to read signals from restless calderas, two as
the different stages and their surface times the amount erupted during the crystals and lake sediment deposits, Calderas appear to be cyclic, but their The M 4.5 1883 eruption of Krakatau is often yet insurmountable challenges are to predict
representations. 1980 eruption of Mt St Helens!), forming revealing that resurgence began at least periodicity varies rapidly. Our best strategy is quoted as the loudest sound ever produced exactly when (if) an eruption will occur and how
a caldera 30 km wide and 100 km 30 ka and continued until at least 2.7 to be vigilant at the currently active systems on Earth. It was apparently clearly heard up to big it will be. Methods and technologies that
NEW RESEARCH FOCUS long. Since then, the caldera floor has ka. Eruptions fed by remnant magma and pay attention to volcanic areas around the 3,000 miles away and the pressure spike (an help answer these two questions are critical.
To specifically improve understanding of experienced well over 1 km of vertical rejuvenated by fresh magma from deep Earth that have shown this type of activity in acoustic wave) created by the eruption was One exciting area of development is the use
resurgence and restlessness, Professor uplift, forming the island of Samosir. This continued for at least 20,000 years after the last two million years or so. recorded around the globe for about five days. of satellites to measure signals associated
de Silva and his team have now turned project, which won the support of the the climactic eruption. New work by So technically the “sound” of this eruption was with volcanoes. Given the global distribution
their attention to Toba, Indonesia. National Science Foundation, aims to graduate students Katharine Solada and What would be some of the local, regional, heard around the world for several days. A of restless calderas and the long time and
Approximately 74 ka (thousand years test the hypothesis that resurgence is fed Jade Bowers is further constraining lake and global impacts of a supereruption supereruption is at least 1000 times as intense spatial scales over which they operate,
ago), Toba experienced the most by magma left over after the climactic sediment history, and expanding our today? as the Krakatau eruption, therefore, the “sound” constant surveillance and measurements by
catastrophic eruption of the last 100,000 eruption. understanding of resurgent eruptions, Our understanding is that everything within a could be expected to be significantly “louder” satellites maybe a key direction in our effort to
years, during which at least 2800 km2 So far, graduate student Adonara Mucek including possible relationships with the 100 km radius will be devastated by pyroclastic and intense. understand supervolcanoes.
of magma was erupted (that is 28,000 has used geochronology to date zircon actively erupting Sinabung volcano.

64 www.researchoutreach.org www.researchoutreach.org 65
Earth and Environment︱ Professor Igor Polyakov NABOS technicians in preparation

One ocean, many minds:


for mooring deployment.

collaborative science in the Arctic

T
The Arctic Ocean is undergoing a period of significant change. In he loss of sea ice in the Arctic
collaboration with an international, multidisciplinary team of scientists, Ocean is a key indicator of
Professor Igor Polyakov from the University of Alaska Fairbanks is the global climate change and is
lead scientist of an observational programme monitoring climatic changes a fundamental issue for modern-day
in the Arctic Ocean. The data he and his team have collected is proving climatology in the polar regions. Data
instrumental in understanding the on-going and fundamental changes collected over the past few decades show
experienced in the Arctic. remarkable changes in Arctic sea ice and
indicate that the Arctic may be entering
a transition period of significant and
potentially irreversible change.

POLAR TRANSITION
Over the last few decades, the extent of
summer sea ice in the Arctic Ocean has
reduced at an average rate of 11% per
decade. In recent years, this reduction
has also been accompanied by a FOCUSING ON CHANGE programme’s conception in 2002, the collected throughout the programme is
reduction in both thickness and maturity: The overarching goal of the NABOS international research team at NABOS analysed to give information on a wide
the Arctic Ocean lost 42% of its multiyear project is to build a cohesive picture carried out Arctic cruises every year. range of oceanographic and climatic
ice (ice that survives at least one Arctic of climatic changes in the Arctic However, since 2013, cruises have been variables including: ocean turbulence,
summer) between 2005 and 2008. Ocean. In order to achieve this goal, run every other year. greenhouse gases, temperature,
the team at NABOS investigate salinity, alkalinity, and ocean currents.
A COLLECTIVE EFFORT FOR multiple oceanographic research The team’s primary monitoring tool When combined, these observations
OBSERVATIONAL DATA areas, including: circulation patterns, consists of an array of moorings provide a broad picture of ocean
In order to track these remarkable changes in thermodynamic state, mixing anchored to the seabed, beneath the activity. This data, collected during
changes within the Arctic Ocean, rates, chemical composition and sea active ice layer. The mooring locations NABOS cruises, is then made publicly
scientists at the University of Alaska ice. The success accessible online
Fairbanks conceived an innovative and of the NABOS and is available
collaborative observational project, programme relies The success of the NABOS programme for analysis by

relies primarily upon the effective


called the Nansen and Amundsen Basins primarily upon researchers across
Observational System (NABOS). the effective the globe.
Established in 2002, NABOS focuses
on the Eurasian basin (comprised of the
collaboration of
scientists from
collaboration of scientists from a wide The collection
Nansen and Amundsen basins) in the a wide range range of countries, institutions and of oceanic data
eastern Arctic and exploits a diverse of countries, at high-latitudes
range of observational methods, such institutions and scientific disciplines is notoriously
as mooring buoys and oceanographic scientific disciplines. challenging,
surveys. As the lead scientist of NABOS, A collaborative approach has been key have been carefully selected to capture with scientists often facing harsh
Professor Igor Polyakov collaborates to obtaining repeated oceanographic key elements of the system, such as working conditions such as snow,
with scientists from several different sections and the long-term maintenance circulation patterns, the interactions ice-cover, poor visibility and negative
countries, collecting vital information of mooring buoys. In response to the between different water masses, and temperatures. Despite these
to document and understand climatic observed dramatic reduction of sea transport in the deep ocean basins and challenges, the NABOS cruises have
changes in the Arctic Ocean. The ice, one focus of the team at NABOS shallow shelf boundaries. collected important data that have
programme also encompasses outreach has been an investigation into the made significant contributions to polar
and education through the support mechanisms behind recent sea-ice Oceanographic surveys onboard state- climatology.
of multiple graduate students and reduction. of-the-art research vessels complement
shipboard summer schools. the mooring-based observations and MAKING CONNECTIONS
OBSERVING TRANSFORMATIONS provide opportunities for retrieval and Since the beginning of the programme,
For the first eight summers following the re-deployment of the moorings. Data NABOS has made several major

66 www.researchoutreach.org www.researchoutreach.org 67
Behind the Bench
findings that have greatly enhanced
our understanding of recent
transformations in the Arctic Ocean. For
instance, NABOS observations were
key to identifying a dramatic warming
of the Arctic Ocean throughout the
2000s, which reached its peak between
2006 and 2008.
Professor Igor Polyakov
E: ivpolyakov@alaska.edu T: +1 907 474 2686 W: http://research.iarc.uaf.edu/NABOS2/index.php
In addition, NABOS observations
collected between 2013 and 2015 have
greatly increased our understanding of
the mechanisms behind recent sea-ice
408 G Akasofu Building Funding Institute, St Petersburg, Russia –
reduction. Atmospheric forcing, through International Arctic Research Center National Science Foundation (NSF) Vladimir Ivanov, Leonid Timokhov
solar heating of surface waters, is University of Alaska Fairbanks • Applied Physics Laboratory,
accepted as a primary contributor to the 1731 South Chandalar Drive Bio University of Washington – Matthew
loss of sea ice. However, recent NABOS Fairbanks, AK 99775 Igor Polyakov is a Physical Alkire, Jamie Morison, John Guthrie
data has revealed a complex secondary USA Oceanographer with more than 30 • Alfred Wegener Institute,
mechanism that is intensifying the years of experience in Polar Science. He Bremerhaven, Germany – Torsten
reduction of Arctic sea ice. Research Objectives earned his first and advanced degrees Kanzow
Professor Polyakov dedicates his in oceanography and mathematics • Norwegian Polar Institute, Tromso,
At intermediate depth, warm saline research interests to the observational in St Petersburg, Russia. He also has Norway – Arild Sundfjord
water from the Atlantic Ocean flows programme NABOS (Nansen and numerous publications related to • Institute of Ocean Sciences, BC
north into the eastern Arctic Ocean. Amundsen Basins Observational high-latitude climate change and air-ice Canada – Eddy Carmack
Heat from this Atlantic water is System), where he is the lead scientist, ocean interactions.
prevented from reaching the surface and is instrumental in improving
as the overlying stratified layer of cold understanding of the ongoing Collaborators
water, the ‘halocline’ (~50-150m depth) fundamental changes in the Arctic. • Arctic and Antarctic Research
provides an effective insulating barrier.
However, in recent years, the halocline
layer has become significantly weaker,

Q&A
resulting in reduced stratification and
prompting transition to a new ocean atmospheric and oceanic forcings, has How have technological
state: without the presence of a strong profound effects on climate as a result. advancements changed the way
halocline layer, heat can be transferred Why is the eastern Arctic an observational data is acquired at
vertically from the underlying warm important place to gather What are the key questions that need high latitudes?
Atlantic water. This enhanced upward observational data? to be addressed in future Arctic Ocean There is great progress in
heat flux has substantially reduced rates Eddy Carmack, a prominent Arctic research? observational techniques used in Arctic
of winter sea-ice formation and has researcher, said that the Amerasian How will the Arctic Ocean physical, research. Continuous observations
contributed to the loss of sea-ice cover Basin is the king of storage whereas chemical and biological components spanning decades are now available
observed over recent years. the Eurasian Basin is the king of flux. respond to climate change? What impact thanks to the progress in this area.
Climatologically, the Amerasian Basin will the high-latitude climate change have Moreover, new technologies now
indeed stores an impressive 12–20 m on lower latitude regions? allow observations which we were just
NABOS of domed liquid fresh water in the
Beaufort Gyre – four to five times more What is next for the NABOS
dreaming of ten years back. Mixing
in the ocean, the impact of physical
observations freshwater than the Eurasian Basin. On programme? processes on the state of biological

collected between
the other hand, the eastern Eurasian There is hope that the programme species (to mention just a few) are the
Basin with its shelves is the transit will continue: only by continuous areas where new technologies play the

2002 and 2015 area for the majority of Arctic riverine


water. The Eurasian Basin provides the
observations can important issues
related to climate change in the Arctic
key role.

have greatly shortest pathway for Arctic fresh water be addressed.


to the sub-polar seas, where weak
increased our stratification leads to deep convection,
Only by continuous observations can
understanding of
a key part of global thermohaline
circulation. The eastern Eurasian Basin
important issues related to climate
the mechanisms as a switchgear, redistributing ice
and fresh water between the eastern
change in the Arctic be addressed
behind recent sea- Above and right: Deployment and recovery of
moorings in the harsh Arctic environment has
and western Arctic in response to

ice reduction always been a challenge.

68 www.researchoutreach.org www.researchoutreach.org 69
B
Earth and Environment ︱ Dr Julie Meachen Dr Julie Meachen rappels
efore the withdrawal of the last

Extinct giants, a new


into Natural Trap Cave
ice age in the late Pleistocene © Justin Sipla
some 10,000 years ago, species
diversity was much richer than it is
today. Many Pleistocene species were
bigger, more varied in appearance and

wolf and the key


roamed in greater numbers than those
we see now. Megafauna – large animals
typically weighing more than 44kg and
iconic to this time – such as mastodons,
dire wolves and sabre-toothed cats,

to understanding
roamed the Earth. Now, these species are
extinct, with climate change being one
of the contributing factors in a complex
extinction event that saw a dramatic loss
of diversity.

climate change
In an attempt to better understand
the factors that influenced this mass
extinction and how climate change
affects animal populations, Dr Meachen
along with co-investigator Dr Alan
Cooper and her collaborative team
have been studying the remains of
After its last excavation in the 1970s, a group of palaeontologists, genetics experts and cavers led by vertebrate megafauna excavated from Natural to an abundance of well-preserved Dr Meachen and her collaborative team
palaeontologist and mammalian carnivore specialist Dr Julie Meachen of Des Moines University, have re-opened Trap Cave in Wyoming, North America. Pleistocene fossils. have been able to assess the anatomy
excavations at Natural Trap Cave (NTC) in North America. During this project, Dr Meachen hopes to uncover the Today, we are experiencing a sixth and appearance of species, their diet
secrets of the mass extinction of the last ice age and give high school students the opportunity to get involved mass extinction, with climate change NTC has protected the wealth of and the environmental conditions
in Palaeontology. and human influence believed to be at skeletons that litter its floor for during a time of rapid climate change.
its heart. The research at Natural Trap thousands of years by keeping This information has helped to broaden
By William Harris (Own work) [CC BY-SA 4.0 (http://creativecommons.

Cave (NTC) could not only uncover temperatures below 10°C and understanding of how animals may have
information about the events leading preventing weathering from wind and responded to environmental changes
to the loss of the ice age’s megafauna, rain. As a result, the fossils recovered brought about by a warming climate,
but may also help us to understand how from the site are often of unusually by revealing immigration patterns and
climate change has played a role in the high quality and many are almost fully changes in anatomy.
org/licenses/by-sa/4.0)], via Wikimedia Commons

current extinction crisis. intact, allowing for a unique look at the


past ecosystems of America. Some of A DIFFICULT WOLF TO CLASSIFY
A GLIMPSE INTO THE PAST the most complete American Cheetah One of the key findings by the team at
Natural Trap Cave is a pit cave in North (Mirancinonyx trumani) specimens have NTC has been that of Beringian wolf
America. During the Pleistocene, this been recovered from this site, as well specimens. The recently classified
natural deadfall trap would have been as an extinct species of Musk-oxen Alaskan Beringian wolf had not
located south of the Cordilleran and (Bootherium bombifrons) and several previously been identified as far south
Laurentide ice sheets– glaciers that were specimens of unclassified wolves. as Wyoming. Researchers who studied
separated by a channel leading from NTC wolves in the past had trouble
Alaska into North categorising the
America. NTC lies skeletons they
just south of where The research at Natural Trap Cave (NTC) uncovered because
this corridor between Beringian wolves
the ice sheets could help us to understand how climate are very similar

change has played a role in the current


would have ended. to both extinct
Previous research Dire wolves (Canis
has revealed that
prey and predator
extinction crisis dirus) and today’s
Grey wolves (Canis
species would lupus). However,
have used this channel as a migration NTC was first revisited in 2014, with by analysing DNA recovered from
route into new territories. During this another two field sessions in 2015 and specimens at NTC, and measurements
migration, some animals would fall into 2016 providing excellent data. Using taken from jaw bones and teeth, Dr
Holocene bison skull from 2016 the cave due to the sheer 85-foot drop. DNA found in the bones and teeth of Meachen’s collaborative team could
Natural Trap Cave excavations.
© Julie Meachen Any animals that managed to survive the long extinct animals, pollen samples and establish that the wolves of NTC are
fall would be unable to escape, leading records from the site’s last excavation, distinct from Dire wolves.

70 www.researchoutreach.org www.researchoutreach.org 71
Behind the Bench
Dr Julie Meachen
E: Julie.Meachen@dmu.edu T: +1 515 271 1568 W: www.dmu.edu/

Dr Julie Meachen Research Objectives Collaborators


Assistant Professor Dr Meachen and her team are currently • Dr Alan Cooper – Australian Centre for
Left: A view of Natural Trap Cave. © Justin Sipla Des Moines University working at Natural Trap Cave, where Ancient DNA (ancient DNA analysis)
Right: An Ice Age coyote jaw from 2016 Natural 3200 Grand Avenue, they are excavating Ice Age mammals • Dr Pennilyn Higgins – U Rochester
Trap Cave excavations. © Julie Meachen Des Moines, IA 50312 to determine how climate change (stable isotope analysis)
USA and the extinction events at the end • Dr Jenny McGuire – Georgia Tech
prey specialists and would have arrived of the Pleistocene (10,000 years ago) (microfaunal analysis)
A little smaller than a Dire wolf and with at NTC by following the migration of Bio have affected the morphology and • Dr Cory Redman – Drake University
Dr Julie Meachen completed her PhD ecology of living and Pleistocene (mammal ecology) – former postdoc
a higher bite force and longer snout to different conditions, such as prey musk-oxen and bison. Dr Meachen
in Ecology and Evolutionary Biology at species. Additionally, they are using • Dr Susumu Tomiya – DMU (mammal
than Grey wolves, Beringian wolves lie availability, differences in temperature believes the migration of Beringian
the University of California in 2008 and a microfaunal and pollen record to morphology & ecology) – current
somewhere between the two species and precipitation rates, they developed wolves into mid-continental America
is now a vertebrate palaeontologist and recreate Pleistocene climate in mid- postdoc
in appearance and are believed to be separate, distinct characteristics. may offer insights into the dispersion
functional morphologist that specialises latitude North America. • Dr Tom Minckley – U Wyoming (pollen
an ecomorph of Canis lupus. In other of the Grey wolf – a species which
in mammalian carnivores at Des Moines analysis)
words, Beringian and Grey wolves were Further study revealed that these once covered the entire Northern University. Funding
the same species, but due to exposure animals were likely to be megafaunal Hemisphere. A last field session in 2017 National Science Foundation (NSF)
promises to further explore how climate
change in the late Pleistocene affected
Dr Meachen believes the migration of these megafaunal populations.

Beringian wolves into mid-continental America BRINGING THE ICE AGE TO SCHOOL

may offer insights into the dispersion of the Barefoot is an educational outreach

Q&A
team looking to make science relatable
Grey wolf – a species which once covered the for children. Founder James MacDiarid able to answer questions about how than ever to pique their curiosity about
has dedicated a decade of his career to climate affects genes, morphology, the natural world and encourage them
entire Northern Hemisphere bringing accurate science to students and the likelihood that a species will go to ask questions about how the world
through videos and video-telecasting. What first interested you in Natural extinct. around them works. I would really
Barefoot’s goal is to encourage children Trap Cave (NTC)? love to inspire future generations of
to ‘Imagine, learn and connect’ with I knew about NTC, but never gave it What can we learn about modern Grey scientists to carry on important work
science using stories to explain complex much thought until I met my Co-PI Dr wolf populations from this research? on climate change and animal/habitat
content. Alan Cooper at a group meeting at the Hopefully this work will give us insights extinctions.
National Evolutionary Synthesis Center into when Grey wolves came into North
In 2016, Barefoot were invited to join Dr in Durham, NC. He suggested we go America, and it has opened the door to What do you hope to achieve with
Meachen and her collaborative team at back to NTC to get ancient DNA from questions about how widespread the your next excavation in 2017?
NTC, where they held skype sessions the source. After that, it took us a few Beringian morph was in North America. We hoped to fill in some gaps in the
with students in Australia and England, tries to get funding, but once we did, It makes me wonder if there are any living microfauna fossil record that we had
bringing the excitement and wonder of the project was off and running. Grey wolves out there that may carry previously missed – and we collected
the ice age directly into the classroom. some hidden Beringian alleles in their about 40 bags of cave dirt to do
It is the hope of both Barefoot and How does your work at NTC change DNA. just that. Hopefully we will get the
the NTC researchers, that by working our understanding of the current microfauna we need! We also were
together to engage with students they extinction crisis and climate change? Why do you think it is important to looking for some good ancient DNA
can provide an insight into how an Our work explores the link between engage children in science? specimens of wolves, coyotes, bison,
excavation is carried out and what it is genetics, morphology, and the Children are the next generation of and horses – and I think we’ve also got
like to uncover the bones of long dead environment. So hopefully we will be adults, and right now, it is more important some good candidates there!
giants.

72 www.researchoutreach.org www.researchoutreach.org 73
Earth and Environment ︱ Edward E. DeLuca
occur when magnetic energy stored in

The Sun’s crowning glory


the corona becomes unstable. Hence,
understanding the coronal magnetic
field will lay the foundation to predict the
volatile nature of the corona.

Observing the corona Forward


RESEARCHING THE SUN
A solar eclipse presents an opportunity
to directly measure the magnetic fields
emanating from the corona. Since
magnetic fields in the corona control the
How do you observe a faint light next to a very bright one? Put simply, with great difficulty. Our knowledge of the origin of the solar wind and the stability
outer atmosphere of the Sun – called its corona – is still fairly limited, due to difficulties observing this part of the of active regions that result in flares and
Sun. Fortunately, solar eclipses (where the Moon and Sun perfectly overlap ‘in syzygy’) provide scientists, such as CMEs, magnetically sensitive infrared (IR)
Dr Edward DeLuca at the Smithsonian Astrophysical Observatory, with an opportunity to explore this unknown lines are the best candidates for making
phenomenon. During the “Great American Eclipse” in 2017, that’s exactly what he did. accurate measurements.

IR is the invisible wavelength radiation


just beyond the red end of the visible
The AIR-Spec on-board the GV aircraft. spectrum. The measurement method
proposed by Dr DeLuca and his

O
team members was to perform IR
ne of science fiction’s greatest very little understanding of the magnetic spectroscopy of the coronal fields. In
and most-beloved movies – field of the corona, which is believed to simple terms, IR spectroscopy passes
2001: A Space Odyssey – opens hold the key to unravelling the mysteries the IR radiation emitted from the corona
by showing a scene where the Sun and of its many solar activities. through a device called a spectrometer
the Moon line up perfectly to form a solar which separates the light into different
eclipse. In August 2017 in America, this Dr Edward DeLuca, from the Smithsonian wavelengths. The resulting signal,
rare phenomenon could actually be seen Astrophysical Observatory (SAO), and detected using a high-resolution
in person. his team of scientists have utilised this camera, produces a spectrum that
rare solar eclipse opportunity to plan and shows absorption and emission lines at
Beyond its aesthetic appeal, a solar execute an experiment that will advance particular IR wavelengths. This data can
eclipse offers a rare opportunity for our knowledge of the Sun’s corona. be analysed to infer detailed information
researchers to observe certain solar and about the corona.
atmospheric phenomena that cannot WHAT GOES ON INSIDE THE
normally be seen because of the Sun’s CORONA? THE AIR-SPEC PROJECT
light. Having the Sun blocked out allows Upon closer examination, the corona, Dr DeLuca and his team proposed the
scientists to explore a relatively unknown composed of hot plasma, is a lustrous Airborne Infrared Spectrometer (AIR-
aspect of the universe we live in – the whorl of solar activity. It is a chaotic Spec) project to maximise the window
Sun’s corona. display of solar flares igniting and of opportunity created by the Great
radiating randomly. Imagine hundreds of American Eclipse. The objective of this
M-M-M-MY SUN’S CORONA fireworks exploding constantly around National Science Foundation (NSF)-
The Sun’s corona is simply its outer the Sun. Energy flows from the corona funded project was to characterise five
atmosphere. This comprises plasma to the photosphere in the form of waves magnetically sensitive coronal emission
that extends hundreds and hundreds as well as heat caused by ‘braiding’ or lines, which are difficult to observe.
of kilometres into space. During a total tangling of magnetic fields in the corona.
eclipse, the Moon Since the
completely obscures spectroscopic
much of the Sun’s During a total eclipse, the Moon signals are very

completely obscures much of the


light, revealing the weak, the AIR-Spec
innermost part of the system had to be
corona – a difficult
thing to observe
Sun’s light, revealing the innermost part extremely stable
and sensitive. As
under ordinary of the corona such, the design and
circumstances. data acquirement
Although scientists instrumentation had
now understand a lot about the make- This heats the corona which accelerates to be meticulously constructed. A large
up of the Sun, there are still many the solar wind. Occasionally, high-energy part of this responsibility fell to Ms Jenna
fundamental questions that have eluded material hurtles across space referred to Samara, a Harvard graduate student and
viable explanation. For instance, we have as coronal mass ejection or CME. These pre-doctoral fellow in Dr DeLuca’s team,

74 www.researchoutreach.org www.researchoutreach.org 75
Behind the Bench
who was instrumental in developing
the apparatus. This kind of teamwork
attitude is something Dr DeLuca feels
strongly adds to his team’s success, citing
Dr Phil Judge from the National Center
for Atmospheric Research’s (NCAR)
High Altitude Observatory (HAO) as a
developer of IR coronal spectroscopy and
Edward E. DeLuca
a key collaborator. E: edeluca@cfa.harvard.edu T: +1 617 496 7725 W: http://hea-www.harvard.edu/~deluca/HomePage.html

At ground level, water vapour in the


atmosphere significantly limits the
Smithsonian Astrophysical Observatory serving as chair of the NASA Heliophysics – Smith College undergraduate, Summer
transmission at certain IR wavelengths. To MS 58, 60 Garden St Division Roadmap committee and as a Intern at SAO; Chad Madsen – Postdoc at
overcome this obstacle, the experiment Cambridge, MA 02138 science editor for the Astrophysical Journal SAO
was devised to be carried out on-board USA for five years. He has had more than 30
an aircraft flying at 45,000–50,000 feet. published papers in the past five years. Research Objectives
To achieve this, Dr DeLuca enlisted Bio Dr DeLuca’s recent project aimed to
the NSF/NCAR Gulfstream-V High- Dr DeLuca is widely recognised for his Collaborators observe five magnetically sensitive
performance Instrumented Airborne Above: The GV aircraft. theoretical work on the magnetic structure Jenna Samra – Harvard U. School of coronal emission lines in the Sun’s
Platform for Environmental Research (GV) Below: AIR-Spec installed, ready for the flight. of solar active regions and magnetic activity Engineering and Applied Science & corona by designing and flying a highly
aircraft (see above image). in the Sun and stars, with work ranging from SAO pre-doc fellow; Phil Judge – High advanced imaging spectrometer to make
instabilities in hot magnetised plasmas Altitude Observatory National Center measurements during the recent 2017 solar
Any sensitive instrument on-board a to magnetic field production in rapidly for Atmospheric Research; Lou Lussier – eclipse.
moving plane experiences fluctuations. rotating convective stars. He has served Research Aviation Facility National Center
Such variations and other vibrations had as the science lead for several missions for Atmospheric Research; Peter Cheimets – Funding
to be tested and dampened to ensure and instrumentation projects. Dr DeLuca CfA Project Engineer/PM; Vanessa Marquez NSF Major Research Instrumentation grant,
satisfactory performance of the AIR-Spec. is active in the Heliophysics community, – CfA Lead Mechanical Engineer; Alisha Vira NSF AGS-1531549
To extract the most data within the

Q&A
short time frame of the solar eclipse, the Is a solar eclipse the only occasion setting/airplane cabin and they need the
flight path of GV was chosen such that when you can perform these coronal software interface to operate remotely
the conditions were favourable for the measurements? Why is that? or via commanding from the ground.
measurements. The instrument design It is not the only occasion; you need to Once we have characterised the emission
included an ephemeris-based (calculated If the footprint of the spectroscopy/ block out the photospheric emission to properties of these coronal lines with
positions of a celestial object at regular imaging apparatus were to be made about ~107. There are telescopes called AIR-Spec, we can understand what would
intervals) GPS pointing and tracking more compact, would that allow for coronagraphs that create artificial eclipses need to be built for a balloon or satellite
system to accommodate this objective. drone type flights? And if so, would using an “occulting” disk to block the and determine if those instruments are
AIR-Spec was designated to fly along that enable better spectroscopic photospheric light. We can’t use one in viable.
a path of maximum eclipse duration. measurements? the GV because the window in the plan
Two separate trial flights were piloted The best option for an autonomous body will cause scattering at a level higher Are models from combustion
in December 2016 and July 2017, after instrument would be on a high-altitude than ~107. The balloon experiment could spectroscopy/coherent anti-Stokes
which, several modifications and fine Dr DeLuca and his team have built a balloon. These can carry heavy support a coronagraph. Also, the new NSF Raman spectroscopy useful in
understanding coronal flares?
highly stable and mobile spectroscopic
tuning were done to better stabilise the instruments, fly at ~150,000 feet and funded 4m Danial K. Inoue Solar Telescope
AIR-Spec. have been successfully used for solar on Maui will be able to observe the solar Probably not, the conditions in the

TAKING FLIGHT
system that can be deployed for various observations in the past. We are in
discussions with colleagues at HAO
corona in the IR without an occulting
disk. That was a huge design challenge.
corona are close to the best vacuums
achievable in the lab. We can detect
The AIR-Spec project took flight at the research efforts about a future balloon project. The University of Hawaii has a prototype signals because of the very long path
onset of the “Great American Eclipse” on 0.5m telescope that has taken these lengths through the coronal structures.
21st August 2017. With the spectrometer Are there other methods you could measurements from Maui. The light emitted is not re-absorbed by
on-board, the GV aircraft set forth LOOKING AHEAD in the South Pacific off the coast of use to measure the spectrum instead gas in front of it, so we see a sum of all
tracing the path of totality of the eclipse. Through AIR-Spec, Dr DeLuca and his Chile is an obvious candidate for future of a spectrometer? Is it safe to assume the technology of the the light emitted along the “line-of-sight”
During the flight, measurements were team have built a highly stable and flights. The emission lines observed by It’s a bit of a tautology – if you are instrumentation (camera/ spectrometer/ – this can be hundreds of megameters in
performed in different parts of the mobile spectroscopic system that the AIR-Spec project will help guide measuring the spectrum it is a stability etc.) is more limiting than the the corona. We have extensive modelling
corona. The GV completed the flight can be deployed for various research future observing programmes. Through spectrometer. Our spectrometer vehicle? Would there be any benefits to of coronal emissions that is constrained
within 10–19 seconds of the projected efforts. The image stabilisation system Dr DeLuca and his collaborator’s uses a grating. There are other types mounting the AIR-Spec on a satellite or by laboratory experiments, atomic
time frame. Analysis of the spectroscopic is independent of the target, so it can work, the Air-Spec project has laid the of spectrometers that use filters or other space vehicles? physics models and solar observations in
data acquired clearly showed the be adapted for any remote-sensing foundations to explore the Sun’s corona interferometric techniques. The NCAR Balloon instrumentation and satellite the EUV and soft X-rays. The same tools
five coronal emission lines that were application. in more detail, thereby expanding our ground-based NAI is a fourier-transform instrumentation are much more expensive can be applied to the IR coronal lines, but
predicted, and a paper detailing the Future eclipse observations are enabled understanding of the Sun, its effects on IR spectrometer that uses interferometry. than airborne instruments. The conditions observations are needed to check on the
results of the AIR-Spec project is due to by the GV’s ability to travel anywhere. Earth and, ultimately, the habitability of that they need to endure are unlike the lab model predictions.
be published later this year. For example, the 2nd July 2019 eclipse our universe.

76 www.researchoutreach.org www.researchoutreach.org 77
Thought Leader

BAS: Investigating icy waters


with Boaty McBoatface
Oceans are not only filled with many weird and wonderful creatures, but they can also slow down climate change – storing
human-produced carbon and heat in their oceanic depths. Understanding how this process happens is vital to predicting
the impact climate change will have over the coming years. Professor Mike Meredith, science leader at the British Antarctic
Survey, focuses on this area – investigating dense waters as they flow from Antarctica into the Atlantic Ocean, as a
participant in the Dynamics of the Orkney Passage Outflow (DynOPO) project.

B
ack in 2014, construction began project was? What was the motivation them when they cross an underwater
on a new polar research vessel for and background of the project, and mountain chain called the South Scotia
for the British Antarctic Survey what was its goal? Ridge. We believe that the contorted
(BAS), to replace two existing ships – the The oceans exert a huge influence on pathways the water takes as it flows over
RRS James Clark Ross and RRS Ernest our planet’s climate, by sucking down and around these mountains leads to a
Shackleton. Fast forward two years, heat and carbon from the atmosphere, lot of mixing, and that this mixing might
and the Natural Environment Research and storing them in the ocean depths for change over time. We hope to find out
Council (NERC), the institution in charge decades or even centuries. This does us exactly how and why this happens, and
of the construction, set up an online poll humans a big favour, by slowing the rate what it means for the role that these deep
asking members of the public to suggest of global warming – but we need to know waters play in climate change.
potential names for this replacement ship. more about how it works, so that we can
predict it better. You recently lived and worked on
The RRS Boaty McBoatface quickly board the British Antarctic Survey
became a firm favourite with the public, A particular focus for us is the waters that (BAS) research ship James Clark Ross.
but ultimately a name was selected that form close to Antarctica. These are made Can you describe what life was like
honours Britain’s much-loved naturalist, Sir incredibly dense by interacting with the there? What did your average day
David Attenborough. Nonetheless, due freezing atmosphere and ice, and they entail? How long were you aboard?
to the widespread publicity received from sink to the seabed and spread out to Actually, I was the unlucky one – whilst I

The DynOPO project has been created to study dense waters


as they flow from the Antarctic into the Atlantic Ocean, and
investigate what happens to them when they cross the South
Scotia Ridge

the naming campaign, the moniker Boaty become the abyssal waters across most of am an Investigator on the project, I was
McBoatface was given to one of the craft’s the globe. These waters have warmed in not participating in the fieldwork myself
underwater vehicles instead. And, in recent decades, and we don’t really know (too many other responsibilities!). But
2017, it embarked on its first mission. why – but we need to figure it out, so that I’ve sailed on the James Clark Ross many
we can better predict how it will change times, so I know what the field party will
Professor Mike Meredith is an in future. This matters for several reasons, have gone through. It’s actually a very
oceanographer and science leader at the including the global heat budget and sea comfortable ship, with all mod cons and
NERC’s BAS. He recently spoke to us at level rise. some of the most advanced science
Research Outreach to discuss his latest equipment that marine scientists could
research venture – the DynOPO project – The DynOPO project was created wish for.
highlighting the impact Boaty McBoatface by scientists at the University of
has had on improving public appreciation Southampton, BAS and the USA to Science expeditions to the Southern
of polar research. study these dense waters as they flow Ocean are hugely exciting of course – not
northward from the Antarctic into the just for the chance to make breakthroughs
Can you explain what the DynOPO Atlantic Ocean, and what happens to in the things we are studying, but also

78 www.researchoutreach.org
Thought Leader

Professor Mike Meredith


of the British Antarctic Survey

because of the environment around us


– the scenery can be amongst the most
spectacular in the world, and the richness
of the wildlife is staggering.

Boaty McBoatface on the deck of the James Clark Ross, prior to the
Life on board typically settles into a routine DynOPO expedition. Photo by Dr. Povl Abrahamsen, BAS
quite quickly, and things tend to revolve
very much around mealtimes. The food
is normally very good, and plentiful –
scientists often leave expeditions several
pounds heavier than when they start! Work
Science expeditions are hugely exciting. The scenery can
will have been full-on – the ship works
around the clock, so the scientists split into
be amongst the most spectacular in the world, and the
shifts, with some working nights to ensure richness of the wildlife is staggering
that data collection never stops. The ship
collected data continuously, even when
it was steaming along between target
sites, but many of the key measurements with a much wider section of the general processes occurring of Antarctica – so having finished
required the ship to be stopped and community than we would otherwise have in the Southern Ocean? my physics degree, I jumped at the
equipment lowered into the ocean, been able to, and explain the science we The Southern Ocean is key to the chance to study for a PhD in Antarctic
sometimes down to a couple of miles are doing to them, and why it matters. functioning of all of Planet Earth. It is oceanography. Soon after that, a job
or deeper. Water samples were collected the main site globally where deep waters became available at the British Antarctic
and analysed in the ship’s laboratories, Can you tell us about some of the other from 1–2 km down rise to the surface and Survey, and the rest is history!
and a great deal of computer-based work The National Oceanography Centre’s Autosub Long-Range (also known research tools and processes you used? can interact with the atmosphere and the
as Boaty McBoatface) being loaded onto the BAS vessel RRS James
was carried out to make sense of all the Clark Ross. Photo by Dr. Povl Abrahamsen, BAS The workhorse of the science we ice; once they have done this, they sink • To find out more information about
data as it was collected. conduct is called a “CTD” (Conductivity- back into the ocean interior for very long the DynOPO Project, or about the BAS
Temperature-Depth instrument). It periods. This means that the Southern in general, please visit their excellent
Expeditions on James Clark Ross are you feel nauseous just by being there. publicity generated by Boaty has had is basically an extremely advanced Ocean can draw down heat and carbon website at www.bas.ac.uk.
typically a few weeks long; the DynOPO It’s also the case that you are working on the research mission? thermometer that is lowered on a wire from the atmosphere much more
was a long one being around seven inclose confines with your colleagues for Boaty was one of the key tools that from the ship down to the seabed. (It also effectively than other regions, and hence
weeks in total. This was excellent – it several weeks, so a lot of tolerance and DynOPO used – it was deployed measures salinity and a number of other can slow the rate of climate change. This
offered scope to collect a huge and patience is required by all. And simply into one of the key deep gaps in the things that we care about.) It collected matters for societies in all parts of the
unique dataset with which we can tackle being away from family and loved ones underwater mountain chain through which samples of water that we brought on- planet, but we need to know more about
the questions we are trying to answer. for such a long period can be emotionally the dense water flowed, and it completed board and measured in the ship’s labs. how it works, so that we can improve
challenging. But typically, a camaraderie missions in and around that gap to collect There are other instruments we used too, how well we can predict it. Professor Mike Meredith
What are the main challenges of develops on-board, and people enjoy data on ocean temperature, how salty it including free-fall probes for measuring British Antarctic Survey
carrying out research in the Antarctic? working together in a team on problems is, how much it is mixing, and so on. By mixing – these are nerve-wracking, And finally, what initially triggered your High Cross, Madingley Road
Antarctic fieldwork in general is that they are all interested in – so whilst being able to stay submerged for days because they aren’t tethered to the ship, interest in polar ocean research? Cambridge CB3 0ET
challenging because of the harshness the challenges are undoubtedly real, or even weeks, it could build up datasets so each deployment is a heart-in-mouth I originally trained as a physicist, which United Kingdom
of the environment, which must be people usually deal with them very well. of a complexity and detail that has never experience. Luckily, they are normally seemed to involve a lot of time spent
treated with utmost respect. Ship-based been possible before – so it enables a real well-trained about coming back when working in darkened laboratories, but I E: information@bas.ac.uk
fieldwork brings its own challenges – Boaty McBoatface was one of the leap forward for the science. The publicity they should. have always been fascinated by extreme
T: +44 (0)1223 221400
the seas around Antarctica can be some research tools at your disposal on surrounding Boaty was wonderful – the environments. Like most people, I was
W: www.bas.ac.uk
of the roughest in the world, so you are this trip. Can you tell us a bit about way it caught the public’s imagination What is the wider significance of amazed by the early documentaries
working in an environment that can make Boaty’s mission? And what impact the gave us scientists the chance to engage understanding the complex physical showing the wildlife and environment

80 www.researchfeatures.com www.researchfeatures.com 81
Biology ︱ Dr Karen Maruska
ACOUSTICS IN CICHLID

Unravelling the signalling


REPRODUCTION
As a postdoctoral scholar at Stanford
University, Dr Maruska used sound
recording analysis to reveal that male

cues controlling vertebrate


cichlids deliberately produce courtship
sounds when close to a gravid female,
and that these sounds are spectrally

reproductive behaviour
compatible with the female’s hearing
abilities. Females were more sensitive
to these sounds when they were gravid,
and this coincided with an increase in
the levels of the primary female sex
hormone estradiol, and an increase

A
in levels of the enzyme that produces
How do vertebrate brains nimals, including humans, live in THERE’S SOMETHING FISHY GOING estradiol (aromatase) in several auditory
integrate information from a multisensory world, using many ON AT LSU processing and decision-making regions
Figure 1- During courtship, males send and females receive different types of information via
external social cues and internal sensory channels to communicate Dr Maruska’s team uses the African multiple sensory channels. Females must then integrate these signals with their own internal in the brain. Behavioural experiments
physiological states to produce during crucial behavioural situations. cichlid fish Astatotilapia burtoni as a physiological state to make context-specific behavioral decisions.. revealed that gravid females were more
appropriate behaviours? This External multisensory or multimodal research model. Fish serve as an excellent attracted to male courtship sounds than
is one of the big questions that signals include: visual, chemosensory model for this work, because they are to unspecific noise, highlighting the
Dr Karen Maruska and her (smell and taste), auditory (sound), the largest and most diverse group of the cichlid brain processes unimodal (mouth brooding), and the young are importance of acoustic cues in female
research team at Louisiana State tactile (touch), and mechanosensory vertebrates, they have well-described and multimodal sensory information, released after approximately two weeks. mate choice.
University (LSU) are striving (e.g., pressure or vibration) cues. These social behaviours, and are easily how sensory systems contribute to
to answer. Dr Maruska leads a signals convey crucial information manipulated during experimentation. behaviour, and how natural fluctuations How do females use male courtship This work provided the first evidence
research group that uses fish about the sender’s status, and must be The availability of such a model provides in the cichlid’s internal hormonal or signals, and where in the female brain for the importance of acoustic
models to investigate how integrated with the receiver’s internal an opportunity to study basic neuron nutritional state can influence neural are these signals integrated with her communication as part of a multimodal
animals process and translate
physiological state for translation into and sensory function, and how these function and behavioural outcomes. internal state to produce appropriate signalling repertoire during cichlid
multisensory social cues into
adaptive behaviours e.g., those involved functions relate to proximate and ultimate In order to uncover new insights into behaviours? In other words, how does reproduction. It also demonstrated that
context-specific behaviours for
in courtship and reproduction. behavioural mechanisms in comparative the mechanisms regulating animal the female decide whether or not perception of such acoustic information
reproduction and survival.
and evolutionary contexts. reproductive behaviour, the team uses to mate with a certain male? These changes, depending on the receiver’s
Specifically, the group studies how a combination of approaches, including: questions are at the centre of Dr internal physiological state (i.e. the
hormonal assays, sound recordings, Maruska’s work. female hormonal state).
advanced microscopy, brain recordings,
Dominant male Astatotilapia burtoni molecular techniques, and behavioural The role of visual signals such as colours THE ROLE OF CHEMOSENSORY
(shown here) are brightly coloured and defend analysis. and the male body quiver in cichlid SIGNALLING IN CICHLID SOCIAL
territories that they use as spawning sites. mating has been intensively studied; INTERACTIONS
Males signal to females during courtship with
visual displays, sounds, chemical cues, and TO MATE OR NOT TO MATE? yet researchers have never been able to Dr Maruska’s research also demonstrated
water movements. These multimodal signals During the reproductive process, a explain the diversity of cichlids by visual that dominant male cichlids modulate
are then used by females to make behavioural
dominant male cichlid fish becomes communication alone. During courtship, their urine release in both reproductive
decisions. Photo credit: Karen Maruska.
brightly coloured and performs female cichlids are exposed to a wide and territorial situations, suggesting
courtship behaviours to tempt passing array of stimuli by dominant males, that urine might be an important social
females into their territories to spawn. A including colours, movements, sounds, signal. Males released urine sooner and
sexually-receptive (gravid) female enters and chemicals, and up until a few years more frequently when visually exposed
the territory, lays eggs, and immediately ago, the role of other sensory channels to gravid females, and the combination
picks them up in her of visual and chemical
mouth. Following signals resulted in ten
this, the male Textbook discussions on the times more courtship

comparative neural control of


quivers his body behaviour than visual
towards the female, cues alone.

communication during reproduction


which results in
her nipping at Along with the
his so-called egg
spots, which look
are essentially non-existent work on acoustic
communication,
remarkably similar these findings further
to female eggs. This act stimulates e.g., the auditory system, was virtually highlight the role of non-visual sensory
the male to release sperm, which then unexplored. The work of Dr Maruska and modalities in reproductive behaviour.
fertilises the eggs already present in the her group has made significant advances Remarkably, reproductive and territorial
female’s mouth. The fertilised eggs are in this area. behaviours were enhanced when males
then reared inside the female’s mouth were simultaneously exposed visually

82 www.researchoutreach.org www.researchoutreach.org 83
acoustic, or visual and chemosensory,
information is conveyed simultaneously,
visual information dominates. The Behind the Bench
Dr Karen Maruska
group is also currently investigating how
anthropogenic noise (noise caused by
humans) might influence fish behaviour,
physiology, and sensory abilities, a E: kmaruska@Isu.edu T: +1 0225 578 1738 W: http://www.lsu.edu/science/biosci/faculty_and_staff/
project led by PhD student Julie Butler. maruska.php W: http://www.kmaruska.biology.lsu.edu/ W: https://burtoniblog.wordpress.com/
This work could have implications for W: https://vimeo.com/182046796 W: https://www.lsu.edu/science/biosci/
how we consider the consequences of
environmental noise, urbanisation, and
climate change on reproduction and Research Objectives Collaborators as vertebrate models to study animal
survival in fishes and other vertebrates. Dr Maruska and her team’s research • Dr Alexandre Nikonov (Louisiana communication, sensory system
aim is to use fish models in order to State University) plasticity, and the neural basis of social
Female cichlids are mouth brooders, gain insight on the basic mechanisms • Dr Suzy Renn (Reed College) behaviours.
and they must be able to rapidly change of how the brain functions and adapts
Figure 2 – The Maruska lab uses an integrative approach that includes behavioural assays, neural
their eating behaviours during the to an animal’s constantly changing Bio Contact
activation, and neural recording studies to investigate where and how unimodal and multimodal external environment and internal Karen Maruska is an Assistant Professor Karen P. Maruska, PhD
sensory information is processed in the fish brain to generate adaptive behaviours in different reproductive cycle. Once brooding
social contexts.
physiological state. of Biological Sciences at Louisiana Assistant Professor
begins, they rapidly cease eating to
State University. She received her PhD Department of Biological Sciences
protect the developing young, and once Funding from University of Hawaii and was Louisiana State University
the young are released, they resume National Science Foundation (NSF) a postdoctoral scholar at Stanford A345 Life Sciences Annex Building,
This work is timely and will transform our eating to regain energy for subsequent
breeding attempts. What controls these
University. Her research uses fishes Baton Rouge, LA 70803, USA

current understanding of how sensory


Q&A
switches, and how exactly does the brain
of pilot studies before deciding on the examining epigenetics, and there are
control the female urge to eat? These
inputs, reproductive state, and behavioural fascinating questions are another current
appropriate experimental protocols to
ensure we collect the most meaningful
likely epigenetic mechanisms involved
in many aspects of this fish’s behaviour
circuits interact in the vertebrate brain NSF-funded focus in Dr Maruska’s group
(in collaboration with Dr Suzy Renn,
Why have you specifically chosen
the African cichlid fish as a model
data possible. Another challenge
is interpreting brain activation data
and physiology. The Fernald Lab at
Stanford University has done some
Reed College), and will shed light on organism for your research? in the fish because their forebrains work on epigenetics in this species, but
and chemically to other fish, as opposed undergraduate researchers) on an the neural basis of feeding and maternal First, they are very social fish with develop differently from that in higher there is certainly lots of opportunity to
to visual exposure alone, demonstrating ambitious National Science Foundation- care behaviours. The answers may even now well-characterised territorial vertebrates like mammals. This makes investigate this in the future.
the power of multimodal signalling funded project that will use behavioural, improve our understanding of human and reproductive behaviours. For it difficult to discuss homologies across
in regulating behaviour. Recent work cellular, and molecular analyses to eating disorders. our sensory work specifically, it’s taxa when it comes to functions of What relevance, if any, can this
done by a PhD student in the lab, shed further light on how multimodal important that they use multisensory specific brain regions, but one goal of research have for fish conservation
communication in different behavioural our work is to make advances on this practices?
Karen Field, has shown that females signals are represented in the brain of The long-term goal of Dr Maruska’s
contexts. They are relatively easy to put front as well. Our work on sensory communication
also use chemosensory signalling in the female cichlid, as a model for all research is to gather a complete picture
in different types of social situations and behaviour can have important
the presence of dominant males and vertebrates. Specifically, this project aims of how a species communicates during to examine neural and physiological To what extent do the behaviours implications for fish conservation,
mouth brooding females (a sign of to identify the neural substrates that reproductive and aggressive contexts correlates of behaviours. There is a observed in the controlled management, and aquaculture. For
aggression), and that this coincides with mediate behavioural decisions based on using multisensory systems, and how this lot of background information on this laboratory environment mimic real- example, environmental changes
activation of highly conserved social the reception of multimodal signals, and sensory processing and behaviour can species from several different research life situations for these fish? associated with climate change,
decision-making regions of the brain. A whether neural activation patterns are be influenced by the animal’s internal labs, making it an important emerging Our experiments are purposely urbanisation, and pollution can
senior research associate in the group, influenced by the female reproductive physiology, such as hormone levels, model in behavioural neuroscience. designed to be close to the natural have detrimental effects on the
Dr Alexandre Nikonov, is also recording state. reproductive state, or social status. All Second, they have a sequenced situations that these fish may encounter ability of fishes to sense and react
from single neurons in these same animals live in a multisensory world, genome, making molecular and genetic in the wild. Neural mechanisms of to prey, predators, and mates, all
brain regions to determine how this Preliminary findings revealed clear sending and receiving information in studies possible, as well as comparative behaviour are only meaningful in the of which is crucial for survival and
and evolutionary research. Having context of the behaving animal, so species persistence. A fundamental
chemosensory information released by differences in brain activation between multiple sensory channels, yet many
resources available from whole animal it is important to keep experimental understanding of how fishes use
females is processed in the male’s brain. females exposed to courting males and previous studies examine only a single
behaviour down to molecular-level variables as close to biologically- different sensory channels for
Coupled with the previous work, these other females, allowing the group to sensory modality at a time. Accounting analyses in a single species allows for relevant as possible. While there are communication and survival is
findings illustrate true chemosensory identify parts of the brain involved in for multisensory signals and inputs significant advances in the fields of always some limitations to conducting a necessary first step towards
communication in both sexes of a single receiving and processing such signals. better represents an animal’s natural social behaviour and communication. experiments in the lab, the reproductive interpreting how they may be affected
fish species, and reveal neural substrates world, providing new meaningful data and aggressive behaviours displayed by environmental disturbances and
(i.e., parts of the brain) that mediate WHAT MIGHT THIS MEAN FOR on how animals use this information What has been the biggest technical by this species are similar in aquaria and how they may be able to adapt. This
sexual and aggressive social behaviours SOCIETY? for behavioural decisions. Deciphering challenge in your research to date? their natural habitat of Lake Tanganyika, can contribute to research-based
in females. Dr Maruska’s work has shown that how all of these processes work will One of the biggest challenges in Africa. guidelines for species management
communication in cichlid fish is significantly advance our understanding sensory behaviour experiments and aquaculture practices to improve
is creating the right experimental Do you have plans to explore the species survival.
MAPPING THE BRAIN’S RESPONSE multimodal and nonredundant in both of how the vertebrate brain regulates
conditions so that the fish behave influence of epigenetics on behaviour
TO MULTIMODAL STIMULI sexes, whereby each sensory channel social behaviours, and will likely overlap
normally while ensuring that the sensory in your model?
Building on previous accomplishments, (visual, acoustic, or chemosensory) with other research disciplines, such as: exposures are correct. We perform lots We have discussed the possibility of
Dr Maruska now leads her team (PhD conveys a distinct message. The psychology, evolution, and cognitive
student Teisha King, and several work also found that when visual and neuroscience.

84 www.researchoutreach.org www.researchoutreach.org 85
Biology ︱ Dr Kirstin Gutekunst Synechocystis sp
PCC 6803

Energising life on earth: Thylakoid membranes


(where photosynthesis takes
place)

the third way


Carboxysome (where CO2-
fixation takes place)

Life on Earth is essentially driven by a circuit


Glycogen (storage form of
of photosynthesis, which uses energy from
carbohydrates)
sunlight to form carbohydrates and carbohydrate

T
oxidation, which releases the stored sun energy
in the form of ATP.
Almost all living organisms on earth get their energy, ultimately, from the he processes of fixing solar energy
Cytoplasm (where glycolytic
sun. Energy is fixed in carbohydrates by plants and cyanobacteria during as carbohydrate by photosynthetic routes, TCA cycle and Calvin-
photosynthesis, then both animals and plants release it by breaking down organisms (cyanobacteria, Benson cycle* are located)

those carbohydrates. Until now, only two main routes of carbohydrate algae and plants), and its subsequent break down glucose: the Embden- *only one enzme of the
breakdown were thought to be present in cyanobacteria and plants. breakdown to release energy, water and Meyerhof-Parnas (EMP) pathway, also Calvin-Benson cycle
However, Dr Kirstin Gutekunst, of Christian-Albrechts-University of Kiel, carbon dioxide, are central to life on called simply ‘glycolysis,’ and the (Rubisco) is located in the
carboxysomes
Germany, has found a third pathway – the Entner-Doudoroff pathway – also earth. They have been subject to great oxidative pentose phosphate (OPP)
plays a vital role in carbohydrate breakdown in cyanobacteria and plants. amounts of scientific study, and it was pathway. However, simpler organisms
thought that the pathways and reactions such as bacteria and archaea are known
of both had been well established. to employ a variety of routes to release as germinating seeds and developing First, the Entner-Doudoroff pathway
However, Dr Gutekunst’s work found energy from glucose. One of these is roots, suggesting an operating Entner- releases less energy from glucose: one
that, at least in cyanobacteria and plants, the Entner-Doudoroff pathway. Doudoroff pathway is present. molecule of the energy currency ATP
one glycolytic route has been previously per glucose molecule, compared to
overlooked. Dr Gutekunst’s team has now found that Using the photosynthetic two in the EMP pathway. Although this
the key enzyme of the Entner-Doudoroff cyanobacterium, Synechocystis, might seem disadvantageous at first
ENERGY FROM THE SUN pathway, known as KDPG aldolase, is in Dr Gutekunst and colleagues have sight, the Entner-Doudoroff pathway
All living organisms need two things fact widespread amongst photosynthetic developed mutants in which each of the has some advantages. The pathways
to survive: a source of energy, and a organisms such as cyanobacteria and
source of organic carbon for building
cells. Both of these are fixed by plants
plants, from mosses to higher plants
including rice, barley, maize, banana,
The previously overlooked Entner-
during photosynthesis – making this potato, spinach, soybean, cotton and Doudoroff pathway is in fact widespread
amongst cyanobacteria and plants
process essential to life on earth. During tobacco. In barley, their analyses have
photosynthesis, energy from sunlight is shown that KDPG aldolase is functional
used to combine water and atmospheric during periods of active growth, such
carbon dioxide into glucose sugars, a three pathways of glucose breakdown by which glucose is built up and broken
form of carbohydrate. The solar energy is disrupted. They found that growth down to some extent overlap, but
becomes stored as chemical energy in in the presence of light and glucose with reactions occurring in opposite
the bonds between carbon, hydrogen, was reduced most significantly in those directions. Thus, during daylight when
and oxygen atoms in the glucose mutants without a functional Entner- photosynthesis is active, the action of
molecules. Doudoroff pathway. This indicates that the EMP or OPP pathways can undo the
the Entner-Doudoroff pathway is not only reactions occurring in photosynthesis,
Glucose and its derivates can go on functional, but is a significant contributor causing futile cycling between the two
to be built into larger molecules, such to growth in Synechocystis. The team is processes. Previously, it was thought
as starch, protein, fat, and even DNA. now working, with Dr Götz Hensel from that cyanobacteria compartmentalise
Alternatively, it can be broken down the Leibniz Institute of Plant Genetics their cellular processes chronologically,
completely again – either within the and Crop Plant Research at Gatersleben, focusing on photosynthesis during
plant or in an animal that has eaten it to develop similar ‘knockout’ mutants in daylight hours and respiration in the
– releasing water, carbon dioxide and, barley to test the significance, behaviour dark, thus avoiding this problem. The
crucially, the stored energy. The energy and requirements of the pathway in big advantage of the Entner-Doudoroff
is released in a molecule known as higher plants. pathway is that it does not overlap with
‘adenosine triphosphate’ (ATP) which is any of the reactions of photosynthesis,
the ubiquitous energy currency of all cells. UNIQUE FEATURES allowing cyanobacteria to break
So, how does the Entner-Doudoroff down glucose and release energy
ENERGY FROM SUGARS Analysing Synechocystis cells under the pathway differ from the other and cellular building blocks during
It has long been known that there transmission microscope can have some two pathways operating to break daylight as well as at night, without risk
surprising results! The big black spots that look
are two different pathways by which like eyes are cyanophycin accumulations (a down glucose? There are two of futile cycling. This was exactly when
animals, cyanobacteria and plants storage form of nitrogen). crucial differences. Gutekunst’s mutant studies showed

86 www.researchoutreach.org www.researchoutreach.org 87
It has been known for a long time that cyanobacteria and plants possess both glycolysis (shown in red) and the oxidative pentose phosphate pathway
(shown in blue) as glycolytic routes. However, the Entner-Doudoroff pathway (shown in green) was previously overlooked.
Behind the Bench
Dr Kirstin Gutekunst
GDH
Glycogen Glucose Gluconate
ATP NAD P+ NAD PH ATP
GP HK GK
ADP ADP CO2
PGM
ZWF GND E: kgutekunst@bot.uni-kiel.de T: +49 431 880 4237 W: http://www.researchgate.net/profile/Kirstin_
Glucose-1P Glucose-6P 6P-Gluconate Ribulose-5P Gutekunst W: http://www.biotechnologie.uni-kiel.de/de/mitarbeiter/kirstin-gutekunst
PGI NAD P+ NAD PH EDD NAD P+ NAD PH RPI RPE RPE

Ribose-5P Xylulose-5P
2K-3D-6P-Gluconate TKT Research Objectives Mayo Roettger, Mohammad R. Hajirezaei, She additionally holds two DFG grants
Fructose-6P
(KDPG) Dr Gutekunst’s work focuses on the Frank D. Sönnichsen, Peter Schönheit, to study the carbon metabolism in
PFK
ATP
Glyceraldehyde-3P Sedoheptulose-7P hydrogen and central carbon metabolism William F. Martin. photoautotrophs. Dr Kirstin Gutekunst
FPB TAL in cyanobacteria and plants, particularly Collaborators: is mother of five children, two of them
ADP EDA
Fructose-6P Erythrose-4P the Entner-Doudoroff pathway – Alexander Makowka, Berit Bünger, studying at University and three of them
Fructose-1,6bP an overlooked glycolytic route in Lars Nichelmann, Dr Götz Hensel, Prof still attending school. Combining family life
Fructose-6P cyanobacteria and plants. Karin Krupinska, Prof Wolfgang Bilger, and science is her passion.
Pyruvate Prof Christoph Wittmann, Prof Karl
Xylulose-5P Funding Forchhammer. Contact
ALD
Glyceraldehyde-3P TKT Deutsche Forschungsgemeinschaft (DFG) Dr Kirstin Gutekunst
TPI (GAP) Bundesministerium für Bildung und Bio Christian-Albrechts-Universität zu Kiel
Forschung (BMBF) Dr Kirstin Gutekunst is a senior scientist Botanisches Institut und Botanischer
DHAP GAPDH
NAD(P)+
in the group of Prof Rüdiger Schulz. Garten
NAD(P)H
Collaborators She was recently awarded with a Kiel
1,3bP-Glycerate
ADP
Cyanobacteria and plants possess Co-authors: Forschungspreis from the BMBF for her Germany
Xi Chen, Karoline Schreiber, Jens Appel, own research. This group aims to maximise
PGK
ATP three alternative glcolytic routes Alexander Makowka, Berit Fähnrich hydrogen production in cyanobacteria.
3P-Glycerate

Q&A
PGAM
Embden-Meyerhof-Parnas pathway (EMP; glycolysis) mutants in which we knocked out all these organisms. This gives us the
Oxidative pentose phosphate pathway (OPP) known glycolytic pathways. To our opportunity to manipulate the
2P-Glycerate
Entner-Doudoroff pathway (ED) surprise, these mutants were still able carbon flow in a desired manner. The
ENO
Why do you think the Entner- to enhance their growth on glucose. Entner-Doudoroff pathway might
Phosphoenolpyruvate Doudoroff pathway has been This was completely contradictory be especially important as it can
ADP overlooked for so long? to what we had expected. So we run in parallel with photosynthesis.
PYK
ATP Protein sequences from many realised that something very basic So it might be advantageous to
Pyruvate Chen et al. PNAS (2016) plants and cyanobacteria have been was missing in the picture that we had overexpress this pathway in order to
available for a long time. However, of the central carbon metabolism in enhance product yield.
pathways and key enzymes are not cyanobacteria.
that Synechocystis released significant becomes permanently incorporated the physiology of this third route,
automatically eye-catching. You need Where do you see your research into
amounts of energy from glucose via the into the host. Interestingly, however, integrating this into a full and complete to search for them. In eukaryotes What role do you think the pathway the Entner-Doudoroff pathway going
Entner-Doudoroff pathway. the pathway is not present in all plant revision of carbon metabolism in (animals and plants) routes of glucose plays in nature...? next?
species. Crucially, it appears to be cyanobacteria and plants. With Prof breakdown were first studied in There is exciting work from Flamholz I feel that it is absolutely essential
SUCCESSFUL SYMBIOSIS missing from the ubiquitous ‘model’ Christoph Wittmann of Saarland animals that lack this pathway. There et al 2013, which states that this to understand the central carbon
One of the outstanding questions plant species, Arabidopsis (thale cress), University, she hopes to clarify the was a paradigm that the Entner- pathway is especially advantageous metabolism of photosynthetic
surrounding the Entner-Doudoroff used for genetic, biochemical and importance of the three different Doudoroff pathway is restricted to when bacteria and archeae are not organisms as basically all life on earth
pathway is why it is found only in physiological studies across the world. mechanisms of glucose breakdown prokaryotes (bacteria and archaea). limited in growth by the ATP yield depends on it. We eat plants, drive
plants and bacteria, never in animals. This may explain why the significance of and the relative carbon fluxes in each, It is furthermore missing in the most of their glycolytic route but instead our cars, aircrafts, and ships and
studied model plant Arabidopsis by protein costs. In photosynthetic heat our houses with fossil fuels that
An evolutionary analysis suggests the pathway has remained overlooked under the full range of conditions that
thaliana. I guess as soon as something organisms such as cyanobacteria are nothing else but fixed carbon
that – like photosynthesis – the for so long. plants and cyanobacteria experience,
is accepted to be completely and plants it seems most likely that from ancient plants. What I find most
Entner-Doudoroff pathway made its from light to dark and nutrient-rich to understood these things are naturally it is important when glucose needs thrilling is to unravel the interplay
way into plants from cyanobacteria Having overturned the paradigm of nutrient‑limited. not questioned any longer. As to be broken down in parallel with of photosynthesis and the Entner-
via a process of ‘endosymbiosis,’ two routes to glucose breakdown long as we do not stumble upon photosynthesis. And this is due to the Doudoroff pathway. It seems that
in which one organism is engulfed in photoautotrophs, Dr Gutekunst The implications of this research extend inconsistencies, we can be collectively fact that only this pathway does not this pathway is physiologically most
by another and part of its genome now wants to elucidate more fully beyond fundamental knowledge to blind to misconceptions. form a futile cycle with the Calvin- important under photosynthetic
important applications, including the Benson cycle of CO2 fixation. conditions. And what I really love is
potential to manipulate plants and What drew you to study this the hypothesis that photosynthesis,
The Entner-Doudoroff pathway was cyanobacteria for biotechnological pathway yourself?
We found the pathway accidentally.
…and how could the pathway be
harnessed by humans?
which is an autotrophic process, might
be less independent than generally
transferred from cyanobacteria to plants
uses, such as producing fuels including
I was interested in studying the If photosynthetic organisms are accepted. It might be that this process
hydrogen (H2) as an energy source,
influence of glycolytic routes in exploited to use the energy of needs support from a constant supply
via endosymbiosis and is especially pharmaceuticals or nutrients. It’s high
time this overlooked metabolic pathway
cyanobacteria on their production of sunlight for the production of fuels, of glucose breakdown. Future work
hydrogen, which is a gas that can be will show if this view is true.
important when photosynthesis is
pharmaceutics, food additives
got a look-in! used as a source of energy in fuel cells. and cosmetics, it is essential to

running
So we started to construct deletion understand the carbon flow in

88 www.researchoutreach.org www.researchoutreach.org 89
Biology ︱ Dr Matt Traxler

Unlocking the chemical


secrets of microbial
conversations
A
Dr Matt Traxler of the ctinomycetes are a group of chemical products to interact with other
University of California, Berkeley, bacteria with a wide variety of bacteria in their communities.
is changing the way we study human uses, but they are best
microbes. Gone are the days of known for producing natural products, A wide variety of gene clusters have
thinking about a single species also known as specialised metabolites, been observed in the genomes of these

© Bailey Bonet
in a pure culture in the lab – such as antibiotics. These microorganisms microbes that would theoretically allow
Traxler and his team of graduate also produce many antifungals and them to produce products that have not
students and postdocs are immunosuppressants, among others. been seen in typical lab settings, the
developing a version of mass Not only are they important for use in majority of which are unknown to us.
spectrometry which promises human health and veterinary practices, Usually, in the laboratory these bacteria
to allow single microbial cells, their natural products are also useful in are studied one species at a time under
and their interactions with other agriculture. Actinomycetes are found in strictly controlled conditions. These
species, to be studied under
a wide range of habitats including soils conditions are radically different to
their natural conditions.
and marine waters, and in association those found in natural settings. Dr
with plant roots and insects. These Traxler and his colleagues see this as
microorganisms rarely exist in single a gap in the study of such microbes
species communities. As a result, – by using traditional means we have
actinomycetes may use their range of been ignoring the importance of their
interactions with the other microbes in that will allow us to study microbes in A Streptomyces coelicolor colony (above)
responds to the presence of another
the communities to which they belong. situ, that is, in the soil, tissues or plant actinomycete, Amycolatopsis sp. AA4 by
High-magnification image of a Streptomyces
roots where they are naturally found. making a red pigmented antibiotic called
coelicolor colony producing aerial hyphae (fuzzy This was highlighted in a major prodiginine. This particular colony of
Streptomyces coelicolor is deficient in its ability
texture) and secreting droplets containing the blue- study in which Dr Traxler and his A CLOSER LOOK to produce a second pigmented compound
pigmented antibiotic, actinorhodin.
colleagues found that the well-studied Dr Traxler and his colleagues have called actinorhodin. This allows the full extent
actinomycete, Streptomyces coelicolor, brought together an interdisciplinary of prodiginine production to be easily seen.
could produce an astounding array approach to this issue, combining
of compounds, but only when it
interacted with other soil microbes.
mass spectrometry, microbial ecology
and microscopy, amongst others, to
The ability to ‘see’ molecules
When studied in interactions with five
other actinomycetes, S. coelicolor
develop an improved methodology of
High Resolution Mass Spectrometry
produced by individual bacterial cells
produced metabolites specific to each (HR-MSI) that will allow them to study will open an exciting new window
onto microbial life
of the five other species which it does microbes at an ecologically relevant
not produce in isolation. These findings scale. In September 2016, the National
suggest that interactions between Science Foundation (NSF) awarded
microbes may be a rich new source for Dr Traxler a research grant of nearly compounds in a biological sample. In It is thought that most microbes outside
discovering useful natural products. $300,000 to fund the ongoing this method, a laser is used to ionise of a lab are found in colonies of less
These metabolites were only observed development of this new technology. molecules from the sample surface. than 100 cells, each of which are around
© Dr Vineetha Zacharia.

in specific combinations of species, Moving the laser in a grid pattern one to five microns in size. A team of
suggesting that microbes in-situ could Matrix assisted laser desorption/ allows researchers to create a profile of researchers in Dr Traxler’s lab, including
produce chemicals we have never seen ionisation time-of-flight (MALDI-TOF) chemicals from each point across the postdoctoral fellow Rita Pessotti, are
in the lab. Since then, Dr Traxler has mass spectrometry imaging (MSI) is a sample. This information is then used to working to refine the resolution of their
been working to develop an improved method that enables researchers to build images depicting the distribution MALDI-TOF apparatus from 10x10
method of mass spectrometry imaging visualise the distribution of chemical of individual chemical species. microns to around three microns.

90 www.researchoutreach.org www.researchoutreach.org 91
Behind the Bench
Dr Matt Traxler
E: mtrax@berkeley.edu T: +1 510 642 8058 W: http://plantandmicrobiology.berkeley.edu/
W: http://traxlerlab.berkeley.edu/

Research Objectives Collaborators aims include integrating metabolomic


Dr Matt Traxler’s research seeks to • Eoin L. Brodie, Deputy Director, Climate and transcriptomic paradigms with the
understand how bacteria interact with and Ecosystem Sciences. Lawrence ultimate goal of understanding the role
one another through natural products Berkeley National Lab of specialised metabolism in bacterial
like antibiotics. Projects in his lab range • Javier A. Ceja-Navarro, Research Scientist, interactions and translating this knowledge
from natural products discovery to Lawrence Berkeley National Laboratory into a platform for natural products
understanding how these molecules shape (LBNL), Earth Sciences Division, Ecology discovery.
microbiomes. A key part of his research Department
involves improving the resolution of • Tom Bruns, Professor, Plant & Microbial Contact
imaging mass spectrometry techniques, Biology, University of California at Matt F. Traxler, PhD
with the aim of someday seeing molecules Berkeley Assistant Professor
produced by individual bacterial cells in Dept. of Plant and Microbial Biology
microbiome contexts. Bio UC Berkeley
Matt Traxler received his BS and PhD Berkeley, California 94720-3102
Funding in microbiology from the University of 311 Koshland Hall
National Science Foundation (NSF) Oklahoma, and was a postdoctoral fellow USA
at Harvard Medical School. His research

© Main: Dr Scott Behie.


Q&A
something to learn from these microbes Scott Behie, and Bridget Hansen are
about how to use antibiotics. focused on understanding the roles of
Dr Matt Traxler examines the alignment natural products in the microbiomes of
of an electrospray ionisation source. Other than the discovery of new Why have these interaction-specific plants and insects. Likewise, Bailey Bonet,
antibiotics, what benefits do you think metabolites taken so long to find? Vineetha Zacharia, and Dylan McClung are
will come of studying microbes at this Like all researchers, we build on the focused on understanding the genetics

The future holds an exciting merger


This improved resolution will allow level? work of those who came before us. For of microbial interactions, and how we
single bacterial cells and the chemicals We know that healthy microbiomes are example, work in the lab of Kenji Ueda at can leverage that information to discover

between the study of microbial


they produce to be studied, not in incredibly important to the fitness of all Nihon University in Tokyo began looking novel compounds. It’s a dynamic time
a large lab culture, but in the plant kinds of organisms, including humans. If at interactions between actinomycetes in microbiology, where we are seeing

interactions, chemistry, and


we want to understand how microbiomes in the early 2000s, and that work an expansion from thinking about how
tissues, soils and even samples from
function, we need to understand how continues to be a big inspiration for us. bacteria function at the molecular level,
the gastrointestinal tracts of mammals the microbes within them interact at the What we have done is bring new mass to thinking about how different bacteria
where they would normally occur.
microbiome function chemical level. Our efforts to push the
limits of imaging mass spectrometry
spectrometry techniques into the picture,
and the chemical diversity we found was
function in communities. Our challenge is
to bring these two worlds together, and
Other improvements are also being will hopefully provide a new way to see really surprising. I also want to give credit I hope the tools we are working on will
made to the methods used in this to make the potentially transformative Dr Traxler seeks to learn why bacteria chemical interactions within microbiomes, to the laboratory of Pieter Dorrestein at facilitate this new synthesis.
which have implications for human, animal, UCSD, where I learned many of these
research, including the optimisation power of micro-scale HR-MSI feasible make compounds like antibiotics. He
and crop health. mass spectrometry techniques. Do you think students at Berkeley
of biological sample preparation for any laboratory with an existing high- hopes that, by answering this question,
Beyond this, I would say that discovering benefit from involving this research in
techniques to maximise the spatial resolution mass spectrometer. new methods of compound discovery Why is it important to understand the natural products from microbes in their classes?
resolution achieved by MSI. These could be formed, helping scientists reasons bacteria make compounds like pure culture yielded an incredible I love working with undergraduate
improvements, once firmly established, CHANGING THE FUTURE OF and doctors design new treatments antibiotics? bounty of therapeutics that sustained students! I teach the microbiology lab
will form the basis of a set of protocols MICROBIOLOGY to minimise the spread of antibiotic Antibiotics are essential to our healthcare us for many decades. As discovering class for majors at UC Berkeley. In this
that other researchers will be able to The Traxler laboratory studies microbial resistant pathogens. system, but their efficacy in the clinic novel compounds has become more class, the students isolate actinomycetes
is always being eroded by spreading challenging, we must innovate, and from their own soil samples, and put
use when studying microbes in this interactions, with an emphasis on
pathogen resistance. Historically, resistant looking at microbial interactions is one them into interactions with each other.
way in the future. The ability to ‘see’ understanding how these interactions Though centred on actinomycetes, pathogens are usually observed within a way we can do that. Actinomycetes are particularly interesting
molecules produced by individual are mediated by natural products like the lessons learned from the work few years of introducing a new antibiotic since they make an incredible array of
bacterial cells will open an exciting antibiotics. Dr Traxler’s lab group is of Dr Traxler and his research team therapy. However, bacteria that make Where would you like to take this compounds, but also because they have
new window onto microbial life. This an interdisciplinary team, including could be applied to countless other antibiotics, like actinomycetes, have research next? very interesting shapes and colours that
will advance our understanding of researchers with expertise in microbial antibiotic-producing microbes. With been producing these compounds for The imaging mass spectrometry tools change when they interact. The emphasis
basic biological mechanisms and genetics, ecology, natural products an ever-increasing number of antibiotic millions of years! And, the advantage to and protocols we are developing may in the class is really on formulating
making these antibiotics is still robust, have many applications in the study of hypotheses and designing experiments
principles that govern the exchange chemistry, and informatics analysis. They resistant pathogens, this innovative
even after all that time. This suggests that microbiomes, and it will be very exciting to test them. I think the students enjoy
of metabolites at the scale of single see that the future holds an exciting research could provide new sources of actinomycetes may use these compounds to see what we can learn with these new having the freedom to explore their own
microbes in their microbiomes – the merger between the study of microbial antibiotics with the potential to save in ways that we do not understand, and tools. The people in my lab are doing ideas, which is what science is all about!
communities and environments in interactions, chemistry, and microbiome numerous lives that would otherwise may be profoundly different than the incredibly exciting, multidisciplinary
which they are found. The ultimate aim function. have gone unnoticed. way we use them in the clinic. We have projects. For example, Rita Pessotti,
of this work in the Traxler laboratory is

92 www.researchoutreach.org www.researchoutreach.org 93
COMMUNICATION
Why science must
combat sensationalism
I remember once whilst flicking through a certain popular newspaper, I noticed a headline claiming that ‘one glass of red
wine a day prevents breast cancer’. Social Media
N
aturally, like anyone, I became
intrigued, and delved right into
the content.
Research actually shows that drinking one
glass per day can be bad for health, and
can actually be a causative effect towards
breast cancer – but that’s beside the point.
next to you to hear some of the scientific
claims that people have heard.

This is why you as a researcher need to


for Scientists
Now, I guess I’m different to most other
readers, as I already have an academic To the average viewer reading this
ensure that your work is represented in a
way that is accurate, true and accessible
RSM was born out of multiple
background in science, so I more-or-less
know how to smell rubbish when it is
extensively exaggerated, fabricated
claim, they may not think to question the
to the general public. With the growth of
modern-day media streams – whether it
conversations with researchers who
staring me in the face. scientific validity behind it and will take it
as fact. Research even shows that people
be Facebook, Twitter, TV, radio, whatever
– information is everywhere, and it is vital
see a real benefit in connecting
Reading the article in front of me, the first
half carried on with the sensationalised
lose their attention as quickly as eight
seconds now, so a lot of readers wouldn’t
that people know what to believe.
with a broad audience over an
theme of red wine as the miracle cure
for breast cancer. Fantastic news if true,
have even reached the paragraph
discussing the actual research itself.
Together, scientists can stop sensationalism.
ongoing basis. Social Media can
but highly doubtful – especially when
included on page 36.
There are so many other examples of this
– you only need to ask the person sitting
now be considered one of the
most prominent and important
With the growth of modern-day media
engagement tools of the modern
streams, information is everywhere, and it
is vital that people know what to believe
era. We help you get the ball rolling
and can even provide long term
It wasn’t until the very last paragraph
that anything of any scientific merit was
Social Media Management support.
included, finally mentioning the actual
research the claim had been based on.
And boy, did the rubbish smell fresh.

The research was actually conducted on


the cells within the skin of a type of grape
used to make a particular type of red wine.
Nowhere in the actual research paper itself
(yes, I checked) did it say anything about

Start your Social Media journey now:


red wine or the influence drinking one
glass a day would make. Nor did

www.researchsocialmedia.com
it specifically mention
breast cancer.

94 www.researchoutreach.org
Partnership enquiries: simon@researchoutreach.com
Careers and guest contributions: emma@researchoutreach.com

www.researchoutreach.org

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