BE 150/Bi 250b Winter 2012

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Systems Biology

Instructors

  • Michael Elowitz (Bi/BE/APh)
  • Richard Murray (CDS/BE)
  • Lectures: MWF 11-12, 200 Broad (tentative)

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

  • 11 Dec 2011: updated syllabus (should be final now)
  • 19 Nov 2011: added TAs; updated schedule
  • 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.

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

There will be two 1-hour lectures each week, as well as a 1-hour recitation section.

Week Date Topic Reading Homework
1
4 Jan
6 Jan
MBE/RMM
Course overview
  • Principles in systems biology

Recitation section:

  • Review: 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:

  • MATLAB tutorial
  • Alon, Ch 2: Transcription networks : basic concepts
  • BFS, Ch 2: Modeling of Core Processes
  • Alon, Ch 3: Autoregulation : a network motif
HW #1
3
16 Jan
18 Jan*
20 Jan*

RMM
Circuit motifs
  • Feedforward loops (FFLs)
  • Phosphorylation cascades
  • Two-component signaling systems
  • Sequestration for ultrasensitivty
  • Goldbeter and Koshland
  • Alon, Ch 6: Network motifs in developmental, signal transduction, and neuronal networks
  • BFS, Ch 3: post-transcriptional regulatoin
HW #2
4
23 Jan
25 Jan

MBE
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

HW #3
5
30 Jan
1 Feb

RMM
Robustness
  • Chemotaxis and perfect adaptation
  • Fold change detection
  • Controls analysis of robustness
HW #4
6
6 Feb*
8 Feb

RMM
Noise
  • Random processes
  • Intrinsic and extrinsic noise
  • Stochastic modeling: master equation, SSA
HW #5
7
13 Feb+
15 Feb

MBE
Burstiness in gene expression and signalling
  • Birth-death processes
HW #6
8
20 Feb
22 Feb
24 Feb

RMM
Patterning
  • Morphogenesis
  • Robust morphagen gradient
  • Proportionality and scaling
HW #7
9
27 Feb
29 Feb*+

MBK
Modeling of complex biological networks (Mary Kennedy)
10
5 Mar
7 Mar
MBE
Fine grain patterns
  • Lateral inhibition
  • Notch-delta
HW #8

Old Announcements