Difference between revisions of "BE 150/Bi 250b Winter 2012"

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(Lecture Schedule)
(Lecture Schedule)
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* Review: differential equations
 
* Review: differential equations
 
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* {{be250c pdf|wi11|caltech/bfs-class-coreproc_01Jan11.pdf|BFS, Ch 2}}: Modeling of Core Processes
 
* {{be250c pdf|wi11|caltech/bfs-class-coreproc_01Jan11.pdf|BFS, Ch 2}}: Modeling of Core Processes
 
* Alon, Ch 3: Autoregulation : a network motif
 
* Alon, Ch 3: Autoregulation : a network motif
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* Alon, Ch 5: Temporal programs and the global structure of transcription networks
 
* Alon, Ch 5: Temporal programs and the global structure of transcription networks
 
* Alon, Ch 6: Network motifs in developmental, signal transduction, and neuronal networks
 
* Alon, Ch 6: Network motifs in developmental, signal transduction, and neuronal networks
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* [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.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.ncbi.nlm.nih.gov/pmc/articles/PMC1855407/ Cyanobacterial clock, a stable phase oscillator with negligible intercellular coupling], M. Amdaoud, M. Vallade, C. Weiss-Schaber, and I. Mihalcescu.  ''Proc Natl Acad Sci'', 104(17):7051–7056, 2007.
 
* [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1855407/ Cyanobacterial clock, a stable phase oscillator with negligible intercellular coupling], M. Amdaoud, M. Vallade, C. Weiss-Schaber, and I. Mihalcescu.  ''Proc Natl Acad Sci'', 104(17):7051–7056, 2007.
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* BFS, Sec 5.4: Bacterial chemotaxis
 
* BFS, Sec 5.4: Bacterial chemotaxis
 
* [http://www.pnas.org/content/97/9/4649.full Robust perfect adaptation in bacterial chemotaxis through integral feedback control], Tau-Mu Yi, Yun Huang, Melvin I. Simon and John Doyle.  ''PNAS'', 97(9):4649-4653, 2000.
 
* [http://www.pnas.org/content/97/9/4649.full Robust perfect adaptation in bacterial chemotaxis through integral feedback control], Tau-Mu Yi, Yun Huang, Melvin I. Simon and John Doyle.  ''PNAS'', 97(9):4649-4653, 2000.
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| HW #4
[http://www.cds.caltech.edu/~murray/wiki/images/d/d4/Hw-4.pdf HW4]
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[http://www.cds.caltech.edu/~murray/courses/bi-be250c/wi11/caltech/hw-4Sol.pdf Solutions]
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* Intrinsic and extrinsic noise
 
* Intrinsic and extrinsic noise
 
* Stochastic modeling
 
* Stochastic modeling
Probabilistic differentiation (?)
 
 
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* BFS, Ch 4 and App C
 
* BFS, Ch 4 and App C
 
* [http://www.sciencemag.org/content/297/5584/1183 Stochastic Gene Expression in a Single Cell], Michael B. Elowitz, Arnold J. Levine, Eric D. Siggia and Peter S. Swain.  ''Science'', 297(5584):1183-1186, 2002.
 
* [http://www.sciencemag.org/content/297/5584/1183 Stochastic Gene Expression in a Single Cell], Michael B. Elowitz, Arnold J. Levine, Eric D. Siggia and Peter S. Swain.  ''Science'', 297(5584):1183-1186, 2002.
 
* [http://www.nature.com/nature/journal/v440/n7082/full/nature04599.html Stochastic protein expression in individual cells at the single molecule level], Long Cai, Nir Friedman and X. Sunney Xie.  ''Nature'', 440:358-362, 2006.
 
* [http://www.nature.com/nature/journal/v440/n7082/full/nature04599.html Stochastic protein expression in individual cells at the single molecule level], Long Cai, Nir Friedman and X. Sunney Xie.  ''Nature'', 440:358-362, 2006.
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| HW #5
[http://www.cds.caltech.edu/~murray/wiki/images/8/8e/Hw-5.pdf HW5]
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[http://www.cds.caltech.edu/~murray/courses/bi-be250c/wi11/caltech/hw-5Sol.pdf Solutions]
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| 7
 
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| 13 Feb+ <br> 15 Feb <br><br> MBK/MBE
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| 13 Feb+ <br> 15 Feb <br><br> MBE
| Modeling of complex biological networks (MBK)
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| Burstiness in gene expression and signalling
Dynamic signal coding
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* PWM
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* FM
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* NFkB example
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* [http://www.nature.com/ng/journal/v36/n2/full/ng1293.html Dynamics of the p53-Mdm2 feedback loop in individual cells], Galit Lahav ''et al''.  ''Nature Genetics'',  36:147-150, 2004.
 
* [http://www.nature.com/ng/journal/v36/n2/full/ng1293.html Dynamics of the p53-Mdm2 feedback loop in individual cells], Galit Lahav ''et al''.  ''Nature Genetics'',  36:147-150, 2004.
 
* [http://www.nature.com/nature/journal/v455/n7212/full/nature07292.html Frequency-modulated nuclear localization bursts coordinate gene regulation], Long Cai, Chiraj K. Dalal and Michael B. Elowitz.  Nature 455:485-490, 2008.
 
* [http://www.nature.com/nature/journal/v455/n7212/full/nature07292.html Frequency-modulated nuclear localization bursts coordinate gene regulation], Long Cai, Chiraj K. Dalal and Michael B. Elowitz.  Nature 455:485-490, 2008.
 
* [http://www.nature.com/nature/journal/v466/n7303/full/nature09145.html Single-cell NF-kB dynamics reveal digital activation and analogue information processing], S. Tay ''et al''.  ''Nature'', 466(7303):267-271, 2010
 
* [http://www.nature.com/nature/journal/v466/n7303/full/nature09145.html Single-cell NF-kB dynamics reveal digital activation and analogue information processing], S. Tay ''et al''.  ''Nature'', 466(7303):267-271, 2010
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* [http://linkinghub.elsevier.com/retrieve/pii/S0959437X04000887 Elucidating mechanisms underlying robustness of morphogen gradients], Avigdor Eldar, Ben-Zion Shilo and Naama Barkai. ''Curr Opin Genet Dev.'', 14(4):435-439, 2004.
 
* [http://linkinghub.elsevier.com/retrieve/pii/S0959437X04000887 Elucidating mechanisms underlying robustness of morphogen gradients], Avigdor Eldar, Ben-Zion Shilo and Naama Barkai. ''Curr Opin Genet Dev.'', 14(4):435-439, 2004.
 
* [http://www.pnas.org/content/107/15/6924.short Scaling of morphogen gradients by an expansion-repression integral feedback control], Danny Ben-Zvia and Naama Barkai.  ''PNAS'',  107(15):6924-6929, 2010.
 
* [http://www.pnas.org/content/107/15/6924.short Scaling of morphogen gradients by an expansion-repression integral feedback control], Danny Ben-Zvia and Naama Barkai.  ''PNAS'',  107(15):6924-6929, 2010.
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| 9
 
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* [http://www.ncbi.nlm.nih.gov/pubmed/9015458 Pattern formation by lateral inhibition with feedback: a mathematical model of delta-notch intercellular signalling], Collier et al. Journal of theoretical biology (1996) vol. 183 (4) pp. 429-46.
 
* [http://www.ncbi.nlm.nih.gov/pubmed/9015458 Pattern formation by lateral inhibition with feedback: a mathematical model of delta-notch intercellular signalling], Collier et al. Journal of theoretical biology (1996) vol. 183 (4) pp. 429-46.
 
* [http://www.ncbi.nlm.nih.gov/pubmed/20418862 Cis-interactions between Notch and Delta generate mutually exclusive signalling states], Sprinzak et al. Nature (2010) vol. 465 (7294) pp. 86-90
 
* [http://www.ncbi.nlm.nih.gov/pubmed/20418862 Cis-interactions between Notch and Delta generate mutually exclusive signalling states], Sprinzak et al. Nature (2010) vol. 465 (7294) pp. 86-90
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| 10
 
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| 5  Mar <br> 7 Mar <br> MBE
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| 5  Mar <br> 7 Mar <br> MBK
| Epistasis and modularity
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| Modeling of complex biological networks (MBK)
* Flux balance analysis and yeast metabolism
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* Antibiotic interactions
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* Principle of monochroniticity (?)
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* [http://www.nature.com/ng/journal/v37/n1/abs/ng1489.html Modular epistasis in yeast metabolism], Daniel Segrè, Alexander DeLuna, George M Church and Roy Kishony.  ''Nature Genetics'',  37:77-83, 2004.
 
 
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Revision as of 18:42, 19 November 2011

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

  • 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
  • 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
HW #2
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

HW #3
5 30 Jan
1 Feb

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

MBE
Noise
  • Random processes
  • Intrinsic and extrinsic noise
  • Stochastic modeling
HW #5
7 13 Feb+
15 Feb

MBE
Burstiness in gene expression and signalling 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*+

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

Old Announcements