Bi/BE 250c Winter 2011

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Systems Biology


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

Teaching Assistants

  • Vanessa Jonsson
  • Fiona Chandra

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.


  • 24 Oct 2010: web page creation


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:

 [BFS]  D. Del Vecchio and R. M. Murray, Biomolecular Feedback Systems. Available online at
 [Klipp]  Edda Klipp, Wolfram Liebermeister, Christoph Wierling, Axel Kowald, Hans Lehrach, Ralf Herwig, Systems biology: a textbook. Wiley, 2009.

Lecture Schedule

Week Date Topic Reading Homework
1 4 Jan
6 Jan
Course overview; gene circuit dynamics
  • Core processes in cells
  • Modeling transcription, translation and regulation using ODEs
  • Negative auto-regulation

Recitation section(s):

  • Ordinary differential equations
  • MATLAB tutorial
  • Alon, Ch 2: Transcription networks : basic concepts
  • BFS, Ch 2: Modeling of Core Processes
  • Alon, Ch 3: Autoregulation : a network motif
2 11 Jan
13 Jan
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
3 18 Jan?
20 Jan
Biological clocks: how to produce oscillations in cells
  • Synthetic oscillators (repressilator, dual-feedback oscillator)
  • Circadian clocks in cyanobacteria
  • Optional: plant clocks/circadian rhythm
4 25 Jan
27 Jan
  • Chemotaxis and perfect adaptation
  • Controls analysis of robustness
5 1 Feb*
3 Feb
  • Random processes
  • Intrinsic and extrinsic noise
  • Stochastic modeling
6 8 Feb*
10 Feb
Dynamic signal coding
  • PWM
  • FM
  • NFkB example
7 15 Feb
17 Feb
  • Morphogenesis
  • Robust morphagen gradient
  • Proportionality and scaling
  • Alon, Ch 8: Robust Patterning in Development
8 22 Feb
24 Feb
Fine grain patterns
  • Lateral inhibition
  • Notch-delta
9 1 Mar
3 Mar
Epistasis and modulatory (Keasling) - ???
10 8 Mar


The final grade will be based on homework and a final exam:

  • Homework (75%) - There will be 9 one-week problem sets, due in class one week after they are assigned. Late homework will not be accepted without prior permission from the instructor.
  • Final exam (25%) - The final will be handed out the last day of class and is due back at the end of finals week. Open book, time limit to be decided (likely N hours over a 4-8N hour period).

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 should reflect your understanding of the subject matter at the time of writing.

No collaboration is allowed on the final exam.

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