Difference between revisions of "BE 150/Bi 250 Spring 2014"

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* [http://www.pnas.org/content/109/21/8346.short Design principles of cell circuits with paradoxical components], Hart, Antebi, Mayo, Friedman, Alon, ''PNAS'', <b>109 (21) </b> 8346-8351 2012.
 
* [http://www.pnas.org/content/109/21/8346.short Design principles of cell circuits with paradoxical components], Hart, Antebi, Mayo, Friedman, Alon, ''PNAS'', <b>109 (21) </b> 8346-8351 2012.
 
<!--
 
<!--
Papers discussed in lecture:
 
 
* [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC349147/?tool=pmcentrez An amplified sensitivity arising from covalent modification in biological systems], Goldbeter A, Koshland DE.  ''Proc. Natl. Acad. Sci. U.S.A.'', 78 (11): 6840–4, 1981.
 
* [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC349147/?tool=pmcentrez An amplified sensitivity arising from covalent modification in biological systems], Goldbeter A, Koshland DE.  ''Proc. Natl. Acad. Sci. U.S.A.'', 78 (11): 6840–4, 1981.
 
* [http://www.nature.com/msb/journal/v5/n1/full/msb200930.html Protein sequestration generates a flexible ultrasensitive response in a genetic network], N. E. Buchler and F. R. Cross.  ''Molecular Systems Biology'', 5:272, 2009.
 
* [http://www.nature.com/msb/journal/v5/n1/full/msb200930.html Protein sequestration generates a flexible ultrasensitive response in a genetic network], N. E. Buchler and F. R. Cross.  ''Molecular Systems Biology'', 5:272, 2009.
Line 104: Line 103:
 
|- valign=top
 
|- valign=top
 
|
 
|
 +
  
 
'''3'''
 
'''3'''
 
| 14 Apr+<br> 16&nbsp;Apr+ <br> MBE?
 
| 14 Apr+<br> 16&nbsp;Apr+ <br> MBE?
| Biological clocks: how to produce oscillations in cells
 
* Plant clocks/circadian rhythm
 
* Synthetic oscillators (repressilator, dual-feedback oscillator)
 
* Circadian clocks in cyanobacteria
 
No recitation
 
|
 
* [http://stke.sciencemag.org/cgi/content/full/sci;321/5885/126 Robust, Tunable Biological Oscillations from Interlinked Positive and Negative Feedback Loops], Tsai, Choi, Ma, Pomerening, Tang and Ferrell. ''Science Signaling'', 321(5885): 126, 2008
 
* [http://www.nature.com/nature/journal/v403/n6767/full/403335a0.html A synthetic oscillatory network of transcriptional regulators], Elowitz and Leibler. ''Nature'', 403:335-338, 2000.
 
* [http://www.nature.com/nature/journal/v456/n7221/full/nature07389.html A fast, robust and tunable synthetic gene oscillator], Stricker, ''et al.''.  ''Nature'',  456:516-519, 2008.
 
BE 150:
 
* {{be150 pdf|sp14|caltech/bfs-class-dynamics_05Jan13.pdf|BFS Ch 3}}: Analysis of Dynamic Behavior
 
** Sections 3.5: Oscillatory Behavior
 
| [http://www.cds.caltech.edu/~murray/courses/be150/sp14/hw3.pdf HW3]
 
* {{be150-sp14 matlab|dde.m}}
 
 
|- valign=top
 
|
 
 
'''4'''
 
| 21 Apr <br> 23 Apr+ <br> MBE?
 
 
| Robustness
 
| Robustness
 
* Chemotaxis and perfect adaptation
 
* Chemotaxis and perfect adaptation
* Fold change detection
+
* Fold change detection, robust linear amplifiers
 
* Controls analysis of robustness
 
* Controls analysis of robustness
 +
* Oxygen Homeostasis via Cosubstrate competition
 +
 
Recitation (1 Feb): sensitivity analysis
 
Recitation (1 Feb): sensitivity analysis
 
*Demo of sensitivity analysis and how to add events in simbio: {{be150-sp14 matlab|I1FFL_sens_event_demo.sbproj}}
 
*Demo of sensitivity analysis and how to add events in simbio: {{be150-sp14 matlab|I1FFL_sens_event_demo.sbproj}}
Line 137: Line 119:
 
|
 
|
 
* Alon, Ch 7: Robustness of protein circuits : the example of bacterial chemotaxis
 
* Alon, Ch 7: Robustness of protein circuits : the example of bacterial chemotaxis
 +
BE 150:
 +
* {{be150 pdf|sp14|caltech/bfs-class-dynamics_05Jan13.pdf|BFS, Ch 3}}: Sec 3.3 (Robustness) and Sec 3.6 (Bifurcations)
 +
* {{be150 pdf|sp14|caltech/bfs-class-chemotaxis_05Jan13.pdf|BFS, Sec 5.2}}: Bacterial chemotaxis
 +
 +
Papers discussed in lecture:
 +
* [http://www.sciencedirect.com/science/article/pii/S0006349513001355 Maintenance of Mitochondrial Oxygen Homeostasis by Cosubstrate Compensation], Kueh HY, Niethammer P., Mitchison TJ. ''Biophys J'', <b> 104 (6)</b> 1338-1348 2013.
 
* H. Kitano, [http://www.ncbi.nlm.nih.gov/pubmed/15520792 Biological robustness], Nat Rev Genet, vol. 5, no. 11, pp. 826–837, Nov. 2004.
 
* H. Kitano, [http://www.ncbi.nlm.nih.gov/pubmed/15520792 Biological robustness], Nat Rev Genet, vol. 5, no. 11, pp. 826–837, Nov. 2004.
 
* N. Barkai and S. Leibler, [http://www.ncbi.nlm.nih.gov/pubmed/9202124 Robustness in simple biochemical networks], Nature, vol. 387, no. 6636, pp. 913–917, Jun. 1997.
 
* N. Barkai and S. Leibler, [http://www.ncbi.nlm.nih.gov/pubmed/9202124 Robustness in simple biochemical networks], Nature, vol. 387, no. 6636, pp. 913–917, Jun. 1997.
 
* (optional) C. V. Rao, J. R. Kirby, and A. P. Arkin, [http://www.ncbi.nlm.nih.gov/pubmed/14966542 Design and diversity in bacterial chemotaxis: a comparative study in Escherichia coli and Bacillus subtilis], PLoS Biol, vol. 2, no. 2, p. E49, Feb. 2004.
 
* (optional) C. V. Rao, J. R. Kirby, and A. P. Arkin, [http://www.ncbi.nlm.nih.gov/pubmed/14966542 Design and diversity in bacterial chemotaxis: a comparative study in Escherichia coli and Bacillus subtilis], PLoS Biol, vol. 2, no. 2, p. E49, Feb. 2004.
BE 150:
+
BE150:
* {{be150 pdf|sp14|caltech/bfs-class-dynamics_05Jan13.pdf|BFS, Ch 3}}: Sec 3.3 (Robustness) and Sec 3.6 (Bifurcations)
 
* {{be150 pdf|sp14|caltech/bfs-class-chemotaxis_05Jan13.pdf|BFS, Sec 5.2}}: Bacterial chemotaxis
 
 
* (optional) O. Shoval, L. Goentoro, Y. Hart, A. Mayo, E. Sontag, and U. Alon, [http://www.pnas.org/content/107/36/15995.long Fold-change detection and scalar symmetry of sensory input fields], Proceedings of the National Academy of Sciences, vol. 107, no. 36, pp. 15995–16000, Sep. 2010.
 
* (optional) O. Shoval, L. Goentoro, Y. Hart, A. Mayo, E. Sontag, and U. Alon, [http://www.pnas.org/content/107/36/15995.long Fold-change detection and scalar symmetry of sensory input fields], Proceedings of the National Academy of Sciences, vol. 107, no. 36, pp. 15995–16000, Sep. 2010.
 +
 
| [http://www.cds.caltech.edu/~murray/courses/be150/sp14/hw4.pdf HW4]
 
| [http://www.cds.caltech.edu/~murray/courses/be150/sp14/hw4.pdf HW4]
 +
 +
|- valign=top
 +
|
 +
 +
'''4'''
 +
| 21 Apr <br> 23 Apr+ <br> MBE?
 +
| Biological clocks: how to produce oscillations in cells
 +
* Plant clocks/circadian rhythm
 +
* Synthetic oscillators (repressilator, phosphorylation oscillator, dual-feedback oscillator (? is the dual feedback osc the same as the relaxation oscilltor)
 +
* Circadian clocks in cyanobacteria
 +
No recitation
 +
|
 +
 +
BE 150:
 +
* {{be150 pdf|sp14|caltech/bfs-class-dynamics_05Jan13.pdf|BFS Ch 3}}: Analysis of Dynamic Behavior
 +
** Sections 3.5: Oscillatory Behavior
 +
Papers discussed in lecture:
 +
* [http://stke.sciencemag.org/cgi/content/full/sci;321/5885/126 Robust, Tunable Biological Oscillations from Interlinked Positive and Negative Feedback Loops], Tsai, Choi, Ma, Pomerening, Tang and Ferrell. ''Science Signaling'', 321(5885): 126, 2008
 +
* [http://www.nature.com/nature/journal/v403/n6767/full/403335a0.html A synthetic oscillatory network of transcriptional regulators], Elowitz and Leibler. ''Nature'', 403:335-338, 2000.
 +
* [http://www.nature.com/nature/journal/v456/n7221/full/nature07389.html A fast, robust and tunable synthetic gene oscillator], Stricker, ''et al.''.  ''Nature'',  456:516-519, 2008.
 +
* [http://www.sciencemag.org/content/318/5851/809 Ordered Phosphorylation Governs Oscillation of a Three-Protein Circadian Clock], Rust MJ, Markson JS, Lane WS, Fisher DS, O'Shea EK. ''Science'', <b> 218 (5851)</b> 809-812 2007.
 +
 +
| [http://www.cds.caltech.edu/~murray/courses/be150/sp14/hw3.pdf HW3]
 +
* {{be150-sp14 matlab|dde.m}}
  
 
|- valign=top
 
|- valign=top

Revision as of 01:03, 28 March 2014

Systems Biology

Instructors

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

Teaching Assistants

  • Victoria Hsiao (BE)
  • Vipul Singhal (CNS)
  • Recitation: Fr 11-12, location TBD

This is the course homepage for BE 150/Bi 250 for Spring 2014. This page contains all of the information about the material that will be covered in the class, as well as links to the homeworks and information about the course projects and grading.

WARNING: This page is still under construction. This banner will be removed when things are finalized.

Lecture Schedule

There will be 2-3 one-hour lectures each week, as well as occasional one-hour tutorials, recitations or journal club.

Week Date Topic Reading Homework

1

31 Mar
2 Apr
MBE/RMM
Course overview, gene circuit dynamics
  • Principles in systems biology
  • Core processes in cells
  • Modeling transcription, translation and regulation using ODEs
  • Negative auto-regulation

Recitation section: 5 Apr

Bi 250b:

  • Alon, Ch 1: Introduction
  • Alon, Ch 2: Transcription networks : basic concepts
  • Alon, Ch 3: Autoregulation : a network motif

BE 150:

  • BFS Ch 1: Introductory Concepts (skim)
  • BFS Ch 2: Modeling of Core Processes
    • Section 2.1: Modeling Techniques (skim)
    • Sections 2.2-2.3: transcription and translation, transcriptional regulation

Papers discussed in lecture:

HW1

2

7 Apr
11 Apr*
RMM
Circuit motifs
  • Feedforward loops (FFLs)
  • Phosphorylation cascades (?)
  • Two-component signaling systems (?)
  • Sequestration and 'futile cycles' for ultrasensitivty
  • Positive feedback for toggle switches, hysteresis and irreversibility
  • Cytokine mediated Population response

Recitation (9 Apr): sample problems

Bi 250b:
  • Alon, Ch 4: The feed-forward loop network motif
  • Alon, Ch 6: Network motifs in developmental, signal transduction, and neuronal networks

BE 150:

  • BFS Ch 2: Modeling of Core Processes
    • Section 2.4: post-transcriptional regulation
    • Section 2.5: cellular subsystems

Papers discussed in lecture:

HW2


3

14 Apr+
16 Apr+
MBE?
Robustness
  • Chemotaxis and perfect adaptation
  • Fold change detection, robust linear amplifiers
  • Controls analysis of robustness
  • Oxygen Homeostasis via Cosubstrate competition

Recitation (1 Feb): sensitivity analysis

  • Alon, Ch 7: Robustness of protein circuits : the example of bacterial chemotaxis

BE 150:

Papers discussed in lecture:

BE150:

HW4

4

21 Apr
23 Apr+
MBE?
Biological clocks: how to produce oscillations in cells
  • Plant clocks/circadian rhythm
  • Synthetic oscillators (repressilator, phosphorylation oscillator, dual-feedback oscillator (? is the dual feedback osc the same as the relaxation oscilltor)
  • Circadian clocks in cyanobacteria

No recitation

BE 150:

  • BFS Ch 3: Analysis of Dynamic Behavior
    • Sections 3.5: Oscillatory Behavior

Papers discussed in lecture:

HW3

5

28 Apr
30 Apr
RMM
Noise
  • Random processes
  • Intrinsic and extrinsic noise
  • Stochastic modeling: master equation, SSA

BE 150:

HW5

6

5 May*
7 May*
RMM
Burstiness in gene expression and signalling
  • Birth-death processes
9 May
Course project discussion with TAs

7

12 May
14 May
MBE
Patterning
  • Morphogenesis
  • Robust morphagen gradient
  • Proportionality and scaling
HW6

NotchDeltaGui.m NotchDeltaGui2.m

8

19 May
21 May
MBE
Fine grain patterns
  • Lateral inhibition
  • Notch-delta

9

23 May
28 May+
30 May*
Project presentations


Course Description

BE 150/Bi 250b is a jointly taught class that shares lectures but has different reading material and homework assignments. Students in BE 150 are expected to have a more quantitative background and the course material includes a combination of analytical and conceptual tools. Students in Bi 250b are expected to have more knowledge of basic biological processes and the course material focuses on the principles and tools for understanding biological processes and systems.

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.

Textbook

The primary text for the BE 150 and Bi 250b is

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

Students in BE 150 should also obtain the following notes (freely downloadable from the web):

 [BFS]  D. Del Vecchio and R. M. Murray, Biomolecular Feedback Systems (available online)
  • Note: these notes are being written and will be updated during the course
  • The public version is missing some copyrighted figures. These are available in the class version.
  • Class version (Caltech access only, 5 Jan 2013): TOC, Ch 1, Ch 2, Ch 3, Ch 4, Sec 5.2, App B, Refs

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

 [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.

Course project

All students enrolled in the course will be expected to participate in a course project, which will be assigned after the fourth week of class. Course projects will generally consist of reviewing one or more papers on a topic that makes use principles and tools discussed in the course. Each project will be undertaking by two students (nominally one from BE 150, one from Bi 250). Topic suggestions are posted here. Students can also propose their own topic of student by preparing a 1-2 page proposal and submitting this to the instructors no later than 4 Feb for consideration.

Course project timeline:

  • 1 Feb (Fri): course projects posted on home page and announced in class
  • 4 Feb (Mon): course project preferences due
  • 6 Feb (Wed): project assignments available
  • 20 Feb (Wed): discussion of course projects with TAs and others
  • 4-13 Mar: course project presentations. 15-20 minutes per project + 5-10 minutes questions.

Course preference instructions

  • Each student should send e-mail no later than 4 Feb (Mon) with the following information
    • Course: (BE 150/Bi 250b/Audit)
    • Up to three project preferences (use titles from project listings)
    • Optional preferred partner (both students should e-mail identical preferences)
  • Students will work in pairs, with most teams consisting of a BE 150 student and a Bi 250b student
  • To propose your own project, please e-mail a 1-2 page proposal in addition to at least two project preferences selected from the list of course projects

Grading

The final grade will be based on biweekly homework sets (75%) and a course project (25%). The homework will be due in class approximately 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. The class project will be assigned and the end of the 5th week of instruction and project presentations will be scheduled for the last two weeks of class.

Collaboration Policy

Collaboration on homework assignments and the course project 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. Your course project presentation to properly acknowledge all source materials.