BE 150/Bi 250b Winter 2012

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Systems Biology

Instructors

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

Teaching Assistants

  • Emzo de los Santos
  • Vanessa Jonsson

Course Description

BE 150: Quantitative studies of cellular and developmental systems in biology, including the architecture of specific genetic circuits controlling microbial behaviors and multicellular development in model organisms. Specific topics include chemotaxis, multistability and differentiation, biological oscillations, stochastic effects in circuit operation, as well as higher-level circuit properties such as robustness. Organization of transcriptional and protein-protein interaction networks at the genomic scale. Topics are approached from experimental, theoretical and computational perspectives.

Bi 250b: 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

  • 2 Oct 2011: 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.

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
MBE/RMM
Course overview
  • Principles in systems biology

Recitation sections (TAs):

  • Ordinary differential equations
2 9 Jan
11 Jan+

MBE
Gene circuit dynamics
  • Core processes in cells
  • Modeling transcription, translation and regulation using ODEs
  • Negative auto-regulation

Recitation sections (TAs):

  • MATLAB tutorial
  • Alon, Ch 2: Transcription networks : basic concepts
  • BFS, Ch 2: Modeling of Core Processes
  • Alon, Ch 3: Autoregulation : a network motif
3 16 Jan*
18 Jan*

RMM
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
4 23 Jan
25 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

5 30 Jan
1 Feb

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

HW4 Solutions

6 Feb*
8 Feb

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

Probabilistic differentiation (?)

HW5 Solutions

7 13 Feb+
15 Feb

MBK/MBE
Modeling of complex biological networks (MBK)

Dynamic signal coding

  • PWM
  • FM
  • NFkB example
8 20 FebX
22 Feb

RMM
Patterning
  • Morphogenesis
  • Robust morphagen gradient
  • Proportionality and scaling
9 27 Feb
29 Feb*+

MBE/RMM
Fine grain patterns
  • Lateral inhibition
  • Notch-delta
10 5 Mar
7 Mar
MBE
Epistasis and modularity
  • Flux balance analysis and yeast metabolism
  • Antibiotic interactions
  • Principle of monochroniticity (?)

Old Announcements