Bi/BE 250c Winter 2011

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Systems Biology

Instructors

  • Michael Elowitz (Bi/APh)
  • Richard Murray (CDS/BE)
  • Lectures: Tu/Th, 1-2:30 pm, 151 Braun

Teaching Assistants

  • Vanessa Jonsson (OH: M 3:30-4:30, Steele 3)
  • Fiona Chandra (OH: W 4:30-5:30, Steele 3)

Course Description

The class will focus on quantitative studies of cellular and developmental systems in biology. It will examine the architecture of specific genetic circuits controlling microbial behaviors and multicellular development in model organisms. The course will approach most topics from both experimental and theoretical/computational perspectives. Specific topics include chemotaxis, multistability and differentiation, biological oscillations, stochastic effects in circuit operation, as well as higher-level circuit properties such as robustness. The course will also consider the organization of transcriptional and protein-protein interaction networks at the genomic scale.

Announcements

  • 20 Jan 2011: HW #3 is now posted
  • ODE and MATLAB Tutorial will be held Friday, Jan 7 at 1 pm in Steele 214
  • 24 Oct 2010: web page creation

Textbook

The primary text for the course (available via the online bookstore) is

 [Alon]  U. Alon, An Introduction to Systems Biology: Design Principles of Biological Circuits, CRC Press, 2006.

The following additional texts and notes may be useful for some students:

 [FBS]  K. J. Astrom and R. M. Murray, Feedback Systems. Available online at http://www.cds.caltech.edu/~murray/amwiki.
 [BFS]  D. Del Vecchio and R. M. Murray, Biomolecular Feedback Systems. Available online at http://www.cds.caltech.edu/~murray/amwiki/BFS.
 [Klipp]  Edda Klipp, Wolfram Liebermeister, Christoph Wierling, Axel Kowald, Hans Lehrach, Ralf Herwig, Systems biology: A textbook. Wiley, 2009.
 [Strogatz]  Steven Strogatz, Nonlinear Dynamics And Chaos: With Applications To Physics, Biology, Chemistry, And Engineering. Westview Press, 2001.

SAMPLE MATLAB ODE FILES: runfun.m fun.m

Grading

The final grade will be based on biweekly homework sets. The homework will be due in class one week after they are assigned. Late homework will not be accepted without prior permission from the instructor.

The lowest homework score you receive will be dropped in computing your homework average. In addition, if your score on the final is higher than the weighted average of your homework and final, your final will be used to determine your course grade.

Collaboration Policy

Collaboration on homework assignments is encouraged. You may consult outside reference materials, other students, the TA, or the instructor. Use of solutions from previous years in the course is not allowed. All solutions that are handed in should reflect your understanding of the subject matter at the time of writing.


Lecture Schedule

Week Date Topic Reading Homework
1 4 Jan
6 Jan

MBE
Course overview; gene circuit dynamics
  • Core processes in cells
  • Modeling transcription, translation and regulation using ODEs
  • Negative auto-regulation

Recitation sections (TAs):

  • Alon, Ch 2: Transcription networks : basic concepts
  • BFS, Ch 2: Modeling of Core Processes
  • Alon, Ch 3: Autoregulation : a network motif

hw1 Solutions

2 11 Jan
13 Jan

MBE
Circuit motifs
  • Finding "motifs"
  • Feedforward loops (FFLs)
  • SIMS and multi-output FFLs
  • Alon, Ch 4: The feed-forward loop network motif
  • Alon, Ch 5: Temporal programs and the global structure of transcription networks
  • Alon, Ch 6: Network motifs in developmental, signal transduction, and neuronal networks

HW2

3 18 Jan
20 Jan

RMM
Biological clocks: how to produce oscillations in cells
  • Synthetic oscillators (repressilator, dual-feedback oscillator)
  • Circadian clocks in cyanobacteria
  • Optional: plant clocks/circadian rhythm

Background slides on modeling and stability

HW3 Solutions

4 25 Jan
27 Jan

RMM
Robustness
  • Chemotaxis and perfect adaptation
  • Controls analysis of robustness

HW4 Solutions

5 1 Feb
3 Feb

MBE
Noise
  • Random processes
  • Intrinsic and extrinsic noise
  • Stochastic modeling

Probabilistic differentiation (?)

HW5 Solutions

6 8 Feb
10 Feb

TAs
Population dynamics and Evolution

HW6

7 15 Feb
17 Feb

MBE
Dynamic signal coding
  • PWM
  • FM
  • NFkB example
8 22 Feb
24 Feb

RMM
Patterning
  • Morphogenesis
  • Robust morphagen gradient
  • Proportionality and scaling

HW7 Solutions

9 1 Mar
3 Mar

RMM
Fine grain patterns
  • Lateral inhibition
  • Notch-delta

HW8

10 8 Mar

MBE
Epistasis and modularity
  • Flux balance analysis and yeast metabolism
  • Antibiotic interactions
  • Principle of monochroniticity (?)

Old Announcements