COURSE SYLLABUS
Molecular Systems Biology I
W4510, Fall
2007
Molecular Systems Biology II
W4511, Spring
2007
Faculty:
Dr. Larry Abbott, Kolb Research Annex,
Rm 759, lfa2103@columbia.edu, 543-5070
Dr. Harmen Bussemaker, 740 Fairchild
Extension, hjb2004@columbia.edu, 4-9932
Dr. Virginia Cornish, Havemeyer Hall,
vc114@columbia.edu, 4-5209
Dr. Julio Fernandez, 1011A Fairchild Center, jfernandez@columbia.edu,
4-9141
Dr. Ruben Gonzalez, Havemeyer Hall,
rlg2118@columbia.edu, 4-1096
Dr. John Hunt, 702 Fairchild Center,
jfh21@columbia.edu, 4-5443
Dr. Dana Pe'er, 813B Fairchild Center,
dpeer@biology.columbia.edu, 4-4397
Dr. Itsik Pe’er, 505 Computer Science
Building, itsik@cs.columbia.edu, 939-7135
Dr. Brent Stockwell, 614A Fairchild
Center, stockwell@biology.columbia.edu, 4-2948
Time
and location:
Classroom: 320 Havemeyer Hall
Class time: Tuesday and Thursday
1:10-2:25 pm
Course
Description: This year-long, four-credits per semester, course will
present a quantitative description of the molecular networks that underlie the
myriad phenotypes in living cells. Topics covered include various
high-throughput technologies (genome sequencing, DNA microarrays, proteomics,
and phenotypic drug screening), transcriptional and post-transcriptional
regulatory networks, synthetic biology, and neural networks. These will be
integrated with introductory lectures on molecular and structural biology,
thermodynamics, statistics, and machine learning. This course will be of
interest to advanced undergraduates as well as beginning graduate students in
Biology, Chemistry, Physics, Engineering, and Computer Science. It is
unapologetically quantitative, interdisciplinary, and rooted in the latest
research areas with a soft focus on cancer. The course is taught by research
scientists active in the various areas that integrate systems biology: from
detecting and manipulating single molecules all the way up to the computational
synthesis of molecular networks. In addition to the lectures on Tuesdays and Thursdays
there will be weekly tutorials designed to clarify the material of the
lectures.
Prerequisites: One year of
Biology and one year of Chemistry (AP in High School and/or at Columbia) or
permission from the instructor.
Reading
Material:
One cutting edge research paper assigned each week. These readings are required for all graduate
students taking this course.
Molecular Systems Biology I, W4510, Fall Semester 2007
Course
director for the Fall of 2007: Harmen Bussemaker.
Week 1 (Sept 3, 2007):
Lecture (Fernandez):
Introduction to systems biology as a new perspective
Lecture (Bussemaker):
Genome sequences, annotation, sequence alignment
Week 2 (Sept 10, 2007):
Lecture (Stockwell): Introduction to
cancer
Lecture (Bussemaker):
Expression profiling and scoring differential expression.
Week 3 (Sept 17, 2007):
Lecture (Bussemaker):
Interpreting expression data using Gene Ontology
Lecture (Pe’er):
Modularity in biology, clustering and probing cancer with gene expression
analysis.
Week 4 (Sept 24, 2007):
Lecture (Bussemaker):
Basics of transcription
Lecture (Hunt):
Solution thermodynamics, Structure-Function-Energy pyramid.
Week 5 (Oct 1, 2007):
Lecture (Hunt):
Physiochemical basis of protein folding & protein interactions
Lecture (Hunt):
Structural biology of protein-DNA interactions: molecular cooperativity as the
foundation of complex regulatory interactions
Week 6 (Oct 8, 2007):
Lecture (Cornish):
Molecular recognition of protein-DNA interactions: from basic principles, to
calculation, to engineering
Lecture (Pe'er):
Network motifs, simple building blocks of complex networks
Week 7 (Oct 15, 2007):
Lecture (Pe’er):
Microscopy-based measurements of transcription, network properties,
just-in-time transcription and the p53-Mdm2 feedback loop
Lecture (Bussemaker): Basics of chromatin structure
Week 8 (Oct 22, 2007):
Lecture (Bussemaker):
High-throughput
TF-DNA interaction measurements and modeling the sequence-specificity
of TFs
Midterm
Exam (Week of Oct 22, 2007)
Week 9 (Oct 29, 2007):
Lecture (Bussemaker):
Modeling the
condition-specific activity of TF's
Lecture (Cornish):
Engineering principles of gene regulatory networks
Week 10
(November 5, 2007):
Lecture (Bussemaker): Comparative genomics of non-coding sequence;
Application to discovering cis-regulatory elements in 3’ UTRs
November 6, Election day, University holiday
Week 11
(November 12, 2007):
Lecture (Pe’er): Evolution of modularity and transcriptional
networks
Lecture (Bussemaker): Inferring mechanisms for mRNA stability
regulation from high-throughput mRNA expression data
Week 12
(November 19, 2007):
Lecture (Gonzalez): Post transcriptional world, the transcriptome,
the RNA world, non-coding RNA, ribozymes, micro RNAs, others?
November 22,
Thanksgiving, University holiday
Week 13
(November 26, 2007):
Lecture (Gonzalez): Overview of translation cycle, biomolecular
players, comparison of prokaryotic/eukaryotic translation cycles. Translation
as an emerging systems biology frontier.
Lecture (Gonzalez): RNA structure, dynamics, and function:
Structures of the ribosome and representative structures of translation
factors. cryo-EM models of translational complexes.
Week 14
(December 3, 2007, last week of classes, 2007):
Lecture (Gonzalez): mRNA as a major regulator of its own
expression: Riboswitches within the 5’-UTR, hairpins and pseudoknots involved
in frameshifting and stop-codon readthrough within the coding sequence, micro
RNAs within the 3’-UTR.
Lecture (Gonzalez): Limitations of transcriptional profiling;
Translational profiling: High-throughput polysomal transcript analysis
Final Exam
(Week of Dec 17, 2007)
Molecular Systems Biology II, W4511, Spring Semester 2008
Course
director for the spring of 2008: Dana Pe'er.
Week 15
(January 21,2008):
Lecture (Gonzalez): Riboswitches, metabolite sensing and
translational control
Lecture (Hunt): Mapping of translational regulation onto the
translation cycle: Comparison of stringent response in E. coli and S. cerevisiae and relationship to deregulation of
translation in tumorgenesis and proliferation.
Week 16
(January 28, 2008)
Lecture (Hunt): Difference Gel Electrophoresis (DIGE) technologies
for high-throughput differential analysis of proteins involved in translation
and translational regulation.
Lecture (Cornish): Directed Evolution of RNA: from SELEX to in vivo incorporation of unnatural amino
acids
Week 17
(February 4, 2008)
Lecture (Cornish): Metabolism, metabolomics, and the importance of
metabolic pathways in post-translational modifications, translational
regulation and cancer
Lecture (Pe’er): “Genetic
Genomics”, Chromatin, and discovery of environmentally regulated connections
between mRNA turnover and translation
Week 18 (February 11, 2008)
Lecture (Pe’er Itsik): Genetics: Tracing of mutations in families
and linkage analysis of disease and
expression traits
Lecture (Pe’er Itsik): Genetic association
studies: mapping variants for common
diseases and expression traits using the general population.
Week 19 (February 18, 2008)
Lecture (Pe’er): Genetic mutations in cancer and connections to
regulation of expression and phenotype, a network based approach
Lecture (Pe’er):
Probing post-translational modifications using antibody arrays and flow
cytometry and applications to cancer.
Week 20
(February 25, 2008)
Lecture (Pe’er):
Reconstructing signaling pathways using Bayesian networks.
Lecture (Pe’er):
Modularity, microRNA analysis, expression and expression signatures in Cancer
Week 21 (March 3, 2008)
Lecture (Stockwell): Signaling networks: growth factor signaling,
amino acid starvation, nuclear hormones
Lecture (Stockwell):
Chemical screens to define signaling pathways
Week 22 (March 10, 2008)
Lecture (Stockwell):
Mechanism of drug action in signaling networks
define signaling pathways
Midterm
Exam (Week of March 10, 2008)
Spring
Break (Week of March 17, 2008)
Week 23 (March 24, 2008)
Lecture (Stockwell):
Genetic, RNAi and genomic and synthetic lethal screens to
Lecture (Stockwell):
The druggable genome
Week 24 (March 31, 2008)
Lecture (Stockwell): Identifying signal transduction pathways using
protein-protein interaction; yeast two-hybrid, mass spec. Building and
analyzing protein networks.
Lecture (Cornish):
Engineering signaling networks with synthetic biology.
Week 24 (April 7, 2008)
Lecture (Fernandez):
Single molecule dynamics: the hope. Markovian two state models in proteins.
Classical thermodynamic views.
Equilibrium assumptions.
Relation between macroscopic and microscopic observations, fluctuation
dissipation theorem. Michaelis-Menten at
the single molecule level
Lecture (Fernandez): Single molecule dynamics: the reality. Static and dynamic disorder in protein
dynamics. Power law distributions.
Statistical tools in single molecule studies; bootstrapping.
Week 25 (April 14, 2008)
Lecture (Gonzalez): Single-molecule approaches in translation and
translational regulation
Lecture (Fernandez):
Reverse engineering of single molecule systems.
Analysis and discussion of two well-known cases, the action potential in
neurons and muscle elasticity in the heart.
Week 26 (April 21, 2008)
Lecture (Abbott): Computations
done by single neurons and synapses.
Integration of inputs, mechanisms of selectivity and neural coding.
Lecture (Abbott):
Mechanisms of memory. How can
biochemical changes at synapses store, maintain and recall memories.
Week 27 (April 28, last week of
classes, 2008)
Lecture (Abbott):
Neural Network Dynamics. Models of
spontaneous activity, the interaction of spontaneous and evoked responses, and
generating temporal sequences for motor action
Lecture (Fernandez):
Course summary
Final
Exam (Week of May 12, 2008)