Syllabus:

CMB551
Cell and Molecular Biology Core Course
Fall 2013

The Cell and Molecular Biology core course (CMB551) offers 24 focus areas covering a wealth of
cell and molecular biology in a flexible modular format. This class is assigned 4 graded credit
hours per semester. The individual modules emphasize either in-depth critical discussion of the
primary literature, an emphasis on developing quantitative/mathematical approaches to the
biology, or both. A module consists of six classes and students select a sequence of six
consecutive modules. Each module contributes 10% of the final grade (60%) with the remaining
40% of the grade deriving from the final symposium.

To help you prepare for each module, the instructors have included a listing of summer
readings. You should complete the readings for your six selected modules during the summer,
in advance of the start of class. All of the readings are either from common textbooks (you can
substitute similar chapters from related textbooks if necessary) or can be accessed as PDFs
from the CMB website: http://cmb.duke.edu/program/cmb-core-courses

It is important that you select additional modules as backup choices, as some of the modules
may be oversubscribed and second year students are given preference in their selections.
Please contact Carol Richardson (cmbtgp@biochem.duke.edu) by August 1st with your module
selections.

There will be a short entrance test on the reading materials for all modules on the first day of
class (Aug 26th); this is to ensure that everyone wishing to take a given module has sufficient
background to benefit from it. The tests are mostly closed book, pass/fail, and will not require
you to go beyond the assigned readings. You only take entrance tests for the modules you wish
to take. If you do not pass, you will have the option of taking a make-up test (oral) with the
module instructor or selecting a different module for that slot and taking another (written) test.
The first module starts Wed., Aug. 28th.

At the conclusion of the class, students form two-person teams and devise a research proposal
that is honed over a two-week period with an assigned faculty coach. Be thinking about this as
the course progresses is there a classmate that you feel you can work very effectively with?
All proposals are presented orally to the entire class (students and instructors) in a symposium
in early December. Again, the proposal grade comprises 40% of the final grade.

Course Directors:
Bernard Mathey-Prevot bernard.mathey-prevot@dm.duke.edu 684-8043 C104A LSRC
Chris Nicchitta
christopher.nicchitta@duke.edu 684-8948 436 Nanaline Duke

MODULE ORGANIZATION AND TOPICS

Module 1
Aug 28 to
Sept 9

A
Lew
Controlling the
Cell Cycle

B
Eroglu
Cell-Cell
Interactions

C
Sherwood
Cell Invasion
Through
Extracellular
Matrix

D
Li
Stem cells and
their molecular
regulation

Module 2
Sept 11 to
Sept 23

Bagnat
Protein and
Lipid Sorting

Buchler
Genetic
switches and
oscillators

Mathey-Prevot
Signaling:
How Activation
Leads to
Specificity

Muoio
Metabolism:
Cell Biology to
Systems

Module 3
Sept 25 to
Oct 7

Johnson
Microscopy in
Cell Biology

Lew/Erickson
The
Cytoskeleton

Arshavsky
The Eye As A
Digital Camera

Bennett
Vertebrate
Plasma
Membrane
Polarity:
Molecules to
Physiology

Module 4
Oct 9 to
Oct 23

Bradrick
miRNA Function in
Gene Expression

Capel
Nuclear
Structure/Gene
Regulation

Hirschey
Regulation of
Mitochondrial
Metabolism

Module 5
Oct 25 to
Nov 6

Erickson
Protein-Protein
Interactions

Kuehn
Cell Biology
from a
Bacterial
Perspective
Soderling
Cell Biology of
the Synapse

Fox
Genome
Instability

Module 6
Nov 8 to
Nov 20

Rathmell/Kornbluth
Cell Death
Mechanisms

MacAlpine
Bioinformatics
and Genomics
for the Biologist

Lechler
Building
Multicellular
Structures

Tracey
Genetics of
Complex Animal
Behaviors
Boyce
Glycobiology

COURSE CALENDAR
Day
Wednesday
Monday
Wednesday
Friday
Monday
Wednesday
Friday
Monday
Wednesday
Friday
Monday
Wednesday
Friday
Monday
Wednesday
Friday
Monday
Wednesday
Friday
Monday
Wednesday
Friday
Monday
Wednesday
Friday
Monday
Wednesday
Friday
Monday
Wednesday
Friday
Monday
Wednesday
Friday
Monday
Wednesday
Friday
Monday
Wednesday
Monday
Thursday
Fri/ Saturday

Date
August 20
August 26
August 28
August 30
September 2
September 4
September 6
September 9
September 11
September 13
September 16
September 18
September 20
September 23
September 25
September 27
September 30
October 2
October 4
October 7
October 9
October 11
October 14
October 16
October 18
October 21
October 23
October 25
October 28
October 30
November 1
November 4
November 6
November 8
November 11
November 13
November 15
November 18
November 20
November 25
November 28
December 6/7

Module
University Graduate Student Orientation
Class Introduction & Entrance Tests
1
1
1
1
1
1
2
2
2
2
2
2
3
3
3
3
3
3
4
4
NO CLASSES FALL BREAK
4
4
4
4
5
5
5
5
5
5
6
6
6
6
6
6
Proposal /Meet with Faculty Coaches
Thanksgiving Holiday
CMB 551 SYMPOSIUM
3

Module Descriptions:
Module 1A: Controlling the Cell Cycle

Instructor: Danny Lew
Summary: The accurate copying of a cell's contents and their distribution to produce two
daughter cells is a stunning feat requiring exquisite coordination. The set of carefully
orchestrated steps by which proliferating cells make copies of themselves constitutes the cell
cycle. In this module, we will discuss landmark papers that established the conserved
mechanisms underlying cell cycle control, as well as recent papers dissecting the control
circuitry.
In addition to learning about a fundamental process, this module will explicitly deal with
strategies for reading primary Journal articles to critically assess the validity of their
conclusions. We will also discuss how to turn cartoon diagrams of regulatory pathways into
equations and graphs producing quantitative predictions of pathway behavior, and address the
importance of feedback pathways and bistable systems in generating sharp transitions in cell
behavior.

Readings: from "The Molecular Biology of the Cell", Alberts et al.
Chapter 17: First part: The Cell Cycle.


Module 1B: Cell-Cell Interactions

Instructor: Cagla Eroglu
Summary: Coordinated communication between individual cells is crucial for their organization
into tissues, organs and systems that comprise the body plan of multicellular organisms. To
orchestrate this complex organization each cell should be capable 1) of exchanging chemical
signals between each other 2) of sensing chemical, physical or mechanical cues from its
immediate environment 3) of integrating these external cues to alter cellular functions.

Membrane proteins are central players in cell-cell interactions. For instance, they form
tight junctions that serve to attach neighboring cells together and prevent passage of
substances between the two cells. Other surface proteins are involved in cell-cell recognition
(e.g. immunological synapse). Other membrane proteins serve functions in communication
between the inside of the cell and the cells immediate environment (e.g. focal adhesions).
The module will encompass cellular and molecular approaches to understand the
components and properties of cell-cell interactions. Examples from the literature will integrate
diverse experimental approaches ranging from genetic screens to biophysics. In this way we
hope to examine intercellular signaling mechanisms from multiple experimental angles.

Readings: from "The Molecular Biology of the Cell", Alberts et al.
Chapter 15: Cell Communication
Chapter 19: Cell Junctions, Cell Adhesion, and the Extracellular Matrix

4

Module 1C: Cell Invasion Through Extracellular Matrix

Instructor: David Sherwood
Summary: Regulated cell invasion through extracellular matrix is crucial for physiological
processes such as immune system function, wound healing and organ development. The same
genetic pathways that drive normal invasion are thought to be co-opted in some of the most
devastating human diseases, such as metastatic cancer. This module will examine our current
understanding of the mechanisms that regulate cell invasion through extracellular matrix, and
the different strategies that cells use to migrate through the diverse types of extracellular
matrix.

Readings:
Cell Migration in a 3D Matrix. Current Opinion in Cell Biology 2005, 17:524-532.


Module 1D: Stem cells and their molecular regulation

Instructor: Chuan-Yuan Li
Summary: In this module, we will read original papers describing the discovery of mouse and
human embryonic stem cells, the invention of methods to reprogram differentiated cells into
induced pluripotent stem cells, and the identification of human cancer stem cells. We will also
discuss several studies that describe the molecular mechanisms regulating normal and cancer
stem cells. We hope to understand some of the basic concepts, important questions, and
unresolved controversies in stem cell biology research.

Readings:
1) Human embryonic stem cells. Journal of Cell Science 113, 5-10 (2000)
2) Induced Pluripotent Stem Cells: Past, Present, and Future. Cell Stem Cell 10, 678-684 (2012);
3) Cancer stem cells: an evolving concept. Nature Reviews Cancer. 12,133-143.


Module 2A: Protein and Lipid Sorting

Instructor: Michel Bagnat
Summary: Proteins and lipids are distributed asymmetrically in cellular membranes and this
asymmetry is critical for the biogenesis and function of cellular compartments and determines
how cells interact with their environment. Asymmetric protein and lipid distribution are
achieved by diverse processes including sorting, retention, and elimination. The understanding
of the principles and mechanisms responsible for protein and lipid sorting remains a work in
progress. We will work our way through some of the key papers that set the field in motion,
evaluate the current status of the field and try to design ways to address fundamental, yet
unanswered questions in this field.


5

Readings:
1) Coordinated protein sorting, targeting and distribution in polarized cells. Nat Rev Mol Cell
Biol. 2008 (11): 833-45.
2) Polarized sorting in epithelial cells: raft clustering and the biogenesis of the apical membrane.
J Cell Sci. 2004 117:5955-64.
3) Sorting of sphingolipids in epithelial (Madin-Darby canine kidney) cells. J. Cell Biol. 1987
105(4):1623-35.
4) Polarized distribution of viral envelope proteins in the plasma membrane of infected epithelial
cells. Cell. 1980 20(1):45-54.


Module 2B: Genetic switches and oscillators

Instructor: Nicolas Buchler
Summary: Genetic switches and oscillators are essential for proper patterning, cell
proliferation, and cellular differentiation in biological systems. This "systems biology" module
will cover the underlying principles behind epigenetic switches (bistability) and clocks
(oscillators) in gene networks. My goal is to make you literate enough to read a "systems
biology" paper, transform the paper's mechanistic model into equations, and use COPASI to run
and critically evaluate the modeling conclusions.

Readings: Alberts et al "The Molecular Biology of the Cell", Chapter 7: Control of Gene
Expression (all sections up to Post-transcriptional Controls).


Module 2C: Signaling: How activation leads to specificity
Instructor: Bernard Mathey-Prevot
Summary: Detection of external cues at the cell membrane sets in motion a cascade of events
that culminates in the deployment of a nuclear program, ensuring the appropriate response of
that cell to an external ligand. Signal propagation is carried by a series of effector proteins that
have been identified through genetic and biochemical approaches and shown to belong to
distinct signal transduction pathways. The dominant view until recently had been to consider
each of these pathway as a separate cassette consisting of tens of core proteins, being highly
compartmentalized, hierarchical, and independent from the rest of the proteome. Recent high-
throughput genetic and biochemical data suggest two major revisions to this traditional,
canonical view: (1) a massive increase in the number of components linked to a particular
pathway and (2) extensive crosstalk between these pathways. This new understanding,
however, raises the important question of how specificity can be achieved in such a highly
interconnected network.
This module will concentrate on general principles of signaling pathways. It will not
dwell on an enumeration of the various components for each pathway. Rather, through
students presentations of primary research articles, we will focus on how experimental
strategies and technical innovations have changed our ability to measure and follow pathway
6

activation. We will discuss various strategies used by the cell to insure specificity, and look into
the increasing role that systems biology and quantitative approaches have had on current views
of signaling networks under normal and disease conditions.

Readings:
1) Domains, Motifs, and Scaffolds: The Role of Modular Interactions in the Evolution and Wiring
of Cell Signaling Circuits. Annu. Rev. Biochem. 75:65580 (2006)
2) Assembly of Cell Regulatory Systems Through Protein Interaction Domains. Science 300:445-
452 (2003)
3) Scaffold Proteins: Hubs for Controlling the Flow of Cellular Information. Science 332:680-686
(2011)


Module 2D: Understanding Metabolic Control: From Cell Biology to Systems Physiology

Instructor: Deborah Muoio
Summary: Control of energy metabolism is accomplished via an intricate network of
interdependent biochemical pathways that encompass various subcellular compartments in
multiple organ sites. Diseases of metabolic dysregulation (e.g. obesity, diabetes, heart disease)
have become increasingly prevalent and now pose an escalating threat to global health.
Development of novel pharmacotherapies to successfully combat this epidemic requires
comprehensive understanding of the metabolic and signaling circuitry controlling energy
homeostasis. This module will cover basic strategies of integrative metabolism; with emphasis
on bridging molecular nutrition to whole body physiology.
Discussions will center on tissue-specific metabolic responsibilities, the resident
machinery that enables these functions, key biochemical junctions and principal regulatory
sites. Examples of specific topic areas to be addressed include; nutrient sensing and
mechanisms of nutrient-induced gene regulation, substrate partitioning between catabolic and
anabolic fates, and inter-organ trafficking of fuels. We will review several landmark discoveries
of the genomics era that have provided a deeper, molecular view of metabolic control.
Additionally, we will critically evaluate recent papers describing gene knockout or transgenic
mouse models that have produced unanticipated metabolic phenotypes.

Readings: from Biochemistry, Sixth Edition 2007 (Stryer)
Chapter 15 Metabolism: Basic Concepts and Design
Chapter 27 Integration of Metabolism


Module 3A: Microscopy in Cell Biology

Instructor: Sam Johnson
Summary: Microscopy has been revolutionized by fluorescence and now provides a vast array
of tools with which to investigate biology. This module will cover the principles and possibilities

of microscopy how microscopes and photon-based imaging systems work and what you can
do with them. How do you visualize the morphology of microscopic objects using light and
fluorescence? Which imaging modality is best for a particular sample? How do you gain
information on the dynamics of systems such as the spatial and temporal patterns of signaling
events? How do you extract quantitative information from images? We will discuss a range of
techniques with a heavy emphasis on imaging living samples from microbes to vertebrate
animals - widefield imaging, optical sectioning by confocals, multi-photon excitation and TIRF,
protein dynamics, choosing and exploiting fluorescent proteins/probes and super-resolution
microscopy. The theory and physical principles of the imaging systems will be explained in the
first half of the module to a level giving understanding of how they work and guidance for
optimal use. The second part of the module will be a mixture of theory and exercises in
FIJI/ImageJ covering the processing, visualization and quantification of microscopy data.

See:http://microscopy.duke.edu/learn/CMB551.html


Readings: from "The Molecular Biology of the Cell", Alberts et al.
Chapter 9 focus on the sections discussing light/fluorescence microscopy.


Module 3B: The Cytoskeleton

Instructors: Danny Lew and Harold Erickson
Summary: The remarkable abilities of eukaryotic cells to change shape, move, and collaborate
to produce multicellular organisms rely on polymer-forming proteins that constitute the
cytoskeleton. In the past few years it has become apparent that such proteins have an ancient
evolutionary pedigree, with bacterial relatives that still perform more limited but related
functions. In this module we will discuss some classic papers (including modern classics) that
applied diverse approaches to figure out how cytoskeletal polymers (actin, microtubules, and
bacterial FtsZ) do the amazing things they do.

Quantitative thinking has been essential in figuring out cytoskeletal principles, and part of our
goal in this module is to illustrate how equations and mathematical arguments have been
enormously useful for distinguishing between models for how cytoskeletal processes work.

Readings: from "The Molecular Biology of the Cell", Alberts et al.
Chapter 16: The Cytoskeleton.

Module 3C: The Eye As A Digital Camera

Instructor: Vadim Arshavsky
Summary: We are well familiar with the metaphor comparing the eye with a photographic
camera. Indeed, both rely on refraction and lenses to form images. What is perhaps less
appreciated is that the eye functions as a digital camera. Information about the surrounding
world reaches the back of the eye in the form of photons of variable wavelength, which are
absorbed by rod and cone photoreceptor cells of the retina. The light-evoked electrical signals
produced by photoreceptors are next processed by a network of retinal neurons, so that
information about each point in visual space becomes digitized and reaches the brain through
multiple channels, each reporting a different feature of the visual world (brightness, contrast,
color, motion, etc.).

In this module, we will follow each step of this analog-to-digital transition by discussing critical
experimental papers in three areas: phototransduction (the transformation of a light signal into
an electrical signal); the functioning of the first synapse in the retina; and the split of visual
information into multiple channels each carried by a highly-specialized type of the retinal
ganglion cells. Our goal would be to integrate the findings of molecular, cellular and
electrophysiological studies into a single big picture of how the retina works.


Readings:
1) Beyond counting photons: trials and trends in vertebrate visual transduction. Burns, M.E.,
Arshavsky, V.Y. Neuron (2005) 48, 387401.
2) Cell populations of the retina: The Proctor Lecture. Masland, R.H. Invest. Ophthalmol. Vis. Sci.
(2011) 52, 4581-4591.



Module 3D: Plasma Membrane Polarity: Molecules to Physiology

Instructor: Vann Bennett
Summary: As metazoans, we all begin as symmetrical unfertilized eggs and end up as
assemblies of highly polarized cells organized into complex three-dimensional tissues. An
essential adaptation underlying this amazing transition from a single cell to a multicellular
organism is the ability to organize the cell surface into discrete micron-scale domains.
Understanding the molecular basis for spatial organization of cells in tissues is still in its infancy,
but lies at a critical interface between cell biology, physiology, and clinical medicine. In this
module we will explore recent breakthroughs revealing a polarity pathway involving Par
proteins that is conserved between nematodes and humans. We also will learn about
physiological roles and conserved mechanisms for assembly of lateral membranes of epithelial
cells, excitable membranes of neurons, and the neuromuscular junction in skeletal muscle.

Readings: from "The Molecular Biology of the Cell", Alberts et al.

Chapters 10, 12, 13, 16, 19.


Module 4A: miRNA Function in Gene Expression

Instructor: Shelton Bradrick

Summary: Micro(mi)RNAs are now widely appreciated to participate in many fundamental
biological processes and their dysregulation has been linked to progression of disease. These
21-23 nucleotide RNAs regulate gene expression in the cytoplasm through direct base pairing
with target mRNAs. Understanding the mechanism(s) by which miRNAs impact mRNA
translation and turnover has been an intense (and contentious) area of study over the last
decade. This module will initially cover general aspects of miRNA biology and mechanisms of
cytoplasmic gene expression regulation. We will then trace the twists and turns of efforts by
many laboratories to unravel the molecular mechanisms by which miRNAs exert their biological
roles.

Readings:
1) Regulation of mRNA translation and stability by microRNAs. Fabian, MR et al. (2010) Ann.
Rev. Biochem. 79:351-379.

2) "The Molecular Biology of the Cell", Alberts et al. Chapter 7: Post-Transcriptional Controls
section.


Module 4B: Cell Biology from a Bacterial Perspective

Instructor: Meta Kuehn
Summary: Bacteria have learned much cell biology during their evolution alongside
eukaryotes. They have established relationships with eukaryotes that range from symbiotic and
amicable to downright lethal. We will explore eukaryotic features and processes taken
advantage of and taken control of by bacteria. We will discuss bacterial-cell membrane
interactions and how these lead to endocytic events by co-opting the signaling and cytoskeletal
dynamics of the cell. We will also observe how intracellular bacteria can propel through the
cytoplasm via comet tails of actin. We will discuss how bacteria can traffic to a safe haven
inside cells. We will further discover how some bacterial products have been exploited for cell-
biological manipulations that help us in the laboratory today.

Readings: from "The Molecular Biology of the Cell", Alberts et al.
Chapter 13: Lysosomes, Endocytosis
Chapter 16: Cytoskeleton (esp. Actin).

10

Module 4C: Nuclear Structure/Gene Regulation

Instructor: Blanche Capel
Summary: Many experimental approaches suggest that gene expression is regulated at the
epigenetic level by elements of nuclear structure. These include chromatin modifications of
both DNA and histones as well as variable aspects of nuclear architecture that may also modify
gene expression. In this module, we will discuss key papers that reveal these levels of gene
regulation.

This is an area of Cell Biology that is relatively new. Much of the work remains controversial and
warrants further testing. We will be learning to approach these exciting papers critically with an
eye to designing experimental ways to test and explore these new ideas.

Readings: from "The Molecular Biology of the Cell", Alberts et al.
Chapter 4: Overall Chromatin Structure (limit to pp. 202-245, 5th edition)
Chapter 7: Overview of Gene Control (limit to pp. 411 -432 in 5th edition)
Chapter 12: Overview of Nuclear Structure (limit to pp. 704-712 in 5th edition)


Module 4D: Regulation of Mitochondrial Metabolism

Instructor: Matthew Hirschey
Summary: This workshop-style module will examine how post-translational modifications can
modulate the structure and function of proteins. Protein phosphorylation, ubiquitination, and
acylation will be covered. As a working example, we will focus on protein acetylation, which has
been shown to modify the majority of metabolic enzymes in the mitochondria. Students will be
exposed to basic mitochondrial biology, including functions and dynamics, and then choose
an enzyme to perform a detailed analysis of acetylation sites. Methods for identifying putative
acetylation sites and performing basic structural analyses will be discussed. Students will then
generate novel predictions as to how acetylation might affect their enzyme of
choice. Strategies for assessing these hypotheses will also be covered. Although the focus will
be on acetylation of mitochondrial proteins, the skills acquired in this module will be
broadly applicable.

Readings:
1) Mitochondrial protein acetylation regulates metabolism. Anderson, K.A., and M.D. Hirschey,
2012, Essays Biochem. 52, 2335.
2) "The Molecular Biology of the Cell", Alberts et al., Ch. 14: pp. 813-840.

11

Module 5A: Understanding and Manipulating Protein-Protein Interactions

Instructor: Harold P. Erickson
Summary: Proteins are the machines of the cells. A few enzymes operate alone, but most
proteins interact with others to form more complex machines. In this unit we will learn the
basic principles of protein-protein interaction and bonding, and address the following
questions.
How big is a protein molecule; how do you determine if it is a monomer or tetramer;
how do you determine its shape? What is the structure of a protein-protein bond? How many
amino acids are in contact? How does the dissociation constant relate to the strength of the
bond? How fast do two proteins form a bond, and once formed how long does the complex
last before it dissociates? If you want to eliminate or reduce a protein-protein bond by
mutagenesis, how many amino acids to you need to change? How do you decide which ones?

Readings: from "The Molecular Biology of the Cell", Alberts et al.
Chapter 3: Proteins. Chapter 2, to review basic biochemistry. Most important is to know the
amino acids, which ones are hydrophobic, hydrophilic, charged.


Module 5B: Cell Biology of the Synapse

Instructor: Scott Soderling
Summary: How the brain is wired during development and how these connections are
modified by experience are fundamental questions of neural cell biology. In this module we will
cover examples of how axons navigate to properly innervate their targets. We will also cover
how the synapse is formed and how the strength of the synaptic connection is modified by
experience. Finally we will investigate how impairments to these processes are the basis to
many neurological disorders.

Readings: from "The Molecular Biology of the Cell", Alberts et al.
Chapter 11: Ion Channels and the Electrical Properties of Membranes.
Chapter 21: Neural Development.


Module 5C: Genome Instability

Instructor: Don Fox
Summary: Protection of the genome is key to maintaining normal cellular function. Numerous
safeguards exist to detect genome alterations and potential cell division errors, thus
maintaining a stable genome. Failure in such regulation leads to genome instability. A variety
of human diseases are derived from genome instability, including diseases of aneuploidy such
as trisomies. Genome instability is also present in cancer, and a current debate in the literature
is whether genome instability is a major cause, rather than a consequence, of cancer.

12

In this module, we will take a look at recent literature on causes and consequences of genome
instability in various model systems and in human disease. In the six papers we will discuss, the
wide range of concepts discussed will include cell cycle checkpoints, aneuploidy, and cancer
genomics. Methods used in the papers will similarly cover a wide range of genetic, molecular,
and cell biological assays. Most importantly, this class is geared towards developing critical
literature analysis skills.

Readings:
1) Causes and consequences of aneuploidy in cancer. Gordon DJ, Reiso B, and Pellman, D.
(2012). Nature Reviews Genetics 13, 189-203.
2) Optional reading (if further background is needed): Alberts et al, Chapter 17 (The cell cycle).


Module 5D: Genetic Control of Complex Animal Behaviors

Instructor: Dan Tracey
Summary: It is easy to accept the fact that certain individual human properties are in large part
genetically determined. We have no difficulty in believing that our eye color, our hair, our
height, or our blood pressure are features that vary due to the exact compliment of inherited
genetic variants. Yet, when it comes to our brains and our behavior, genetic determinism
becomes more difficult to accept and is highly controversial. Do behavior genes exist? How
would one define a gene as a behavioral gene? These are some of the questions that we will
attempt to answer in this module. First, we will review the literature that demonstrates
concrete examples of how single genes can affect behaviors. We will examine the evidence
from simple animals such as insects and in rodent models. Finally, we will examine the
evidence that specific gene variants can affect human behavior.
Readings:
1) Are complex behaviors specified by dedicated regulatory genes? Reasoning from Drosophila.
Baker BS, Taylor BJ, Hall JC. Cell. 2001 Apr 6;105(1):13-24. Review.
2) Enhanced partner preference in a promiscuous species by manipulating the expression of a
single gene. Lim MM, Wang Z, Olazbal DE, Ren X, Terwilliger EF, Young LJNature. 2004 Jun
17;429(6993):754-7.
3) The neurobiology of love. Zeki S. FEBS Lett. 2007 Jun 12;581(14):2575-9.


Module 6A: Cell Death Mechanisms
Instructor: Jeff Rathmell and Sally Kornbluth

Cell death is an integral component of development and tissue homeostasis both in health and
disease. Apoptosis is a primary mechanism of programmed cellular suicide wherein cells are
removed from the midst of living tissues without destroying overall tissue architecture. Recent
discoveries have shown that apoptotic cell death is critical for normal development and
immune system functioning. Moreover, inhibition of apoptosis is a hallmark of most cancers
13

and is a key contributor to chemoresistance during cancer treatment. Excess apoptosis is

believed to underlie a number of degenerative disorders of the nervous and musculoskeletal
systems. In addition to apoptosis, alternative pathways for cell death regulation, including
necrosis or autophagy have also been shown to play key roles to determine cell fate.
This module will explore the fundamental cell biology and biochemistry of apoptosis and will
examine physiological processes that depend on apoptosis and pathological processes where
aberrant regulation of cell death contributes to disease.

Readings:
1) Mitochondria and cell death: outer membrane permeabilization and beyond. Nature Reviews
Molecular Cell Biology 11, 621632
2) Molecular Biology of the Cell (Alberts et al):
Chapter 17 The Cell Cycle and Programmed Cell Death (second half on Programmed cell death
and extracellular control of Cell division, cell growth and apoptosis).


Module 6B: Bioinformatics and Genomics for the Biologist

Instructor: David MacAlpine
Summary: Computational biology and genomics are now a mainstay of modern biology. For
example, sequence alignments, identification of gene orthologs and paralogs by blast searches,
and motif identification are now routine practices in the laboratory. In addition, the explosion
of whole genome sequencing in the last decade has led to a variety of genomic approaches
(many based on microarray technology) to phenotype the cell at the level of gene expression
and identify networks of co-regulated genes. These computational tools and genomic
approaches are likely to be integral components of many research projects.
The first part of this module aims to introduce and explain the algorithms behind
common bioinformatic tools, such as global and local sequence alignments, motif finding, and
clustering. In the second part of the module, we will use primary literature to evaluate
genomic strategies for analyzing gene expression, transcription factor binding, and chromatin
modification. The student will not only learn to critically evaluate these complex genomic
experiments, but will also gain first hand experience at analyzing primary microarray data.

Readings:
1) Where did the BLOSUM62 alignment score matrix come from? Eddy, S.R. Nature
Biotechnology 22: 1035-6, 2004.
2) Getting the noise out of gene arrays. Marshall, E. Science 306: 630-1, 2004.
3) Computational analysis of microarray data. Quackenbush, J. Nature Reviews Genetics 2: 418-
427, 2001





14

Module 6C: Building Multicellular Structures: Cell-Cell and Cell-Matrix Adhesion

Instructor: Terry Lechler
Summary: As life became multicellular, cells evolved the ability to organize into functional
three-dimensional structures. This requires cell adhesion, which is necessary for the formation
of tissues and organs. Cell adhesion is required for proper cell shape, cytoskeleton organization,
cell polarity, growth control, and cell migration. We will focus on the basics mechanisms of cell
adhesion and see how they function in normal development, in physiology, and in human
disease.
Class will consist largely of discussions of primary research papers with short
background lectures. The papers discussed will cover classic work in the field as well as new
advances, and will highlight a range of approaches (genetics, biochemistry, imaging, etc).
Emphasis will be placed not only on understanding the scientific findings, but also on critical
reading of articles and understanding the methodologies.

Readings: from "The Molecular Biology of the Cell", Alberts et al.
Chapter 16: The Cytoskeleton
Chapter 19: Cell Junctions, Cell Adhesion and the Extracellular Matrix.


Module 6D: Glycobiology
Instructor: Mike Boyce
Summary: Glycosylation is ubiquitous in all kingdoms of life and impacts on every major cell
biological process. In addition, modern glycobiology has important implications not only for
human health, but also for disparate fields such as renewable energy and materials science. In
recent years, new experimental approaches and technologies have dramatically altered our
understanding of glycobiology, empowering the field as never before. This module will sample
papers from a range of glycobiology topics, with an emphasis on protein glycosylation in
mammalian health and disease. Our goals will be to gain an overview perspective on
glycobiology, learn about the wide variety of techniques used in modern glycosciences, and
hone our critical reading skills.
Readings: Chapter 1 of Varki et al., Essentials of Glycobiology, available at
http://www.ncbi.nlm.nih.gov/books/NBK1931/ for on-line reading.

15