View source for Bi/BE 250c Winter 2011

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<font color='blue' size='+2'>Systems Biology</font>__NOTOC__
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'''Instructors'''
* Michael Elowitz (Bi/APh)
* Richard Murray (CDS/BE)
* Lectures: Tu/Th, 1-2:30 pm, 151 Braun
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'''Teaching Assistants'''
* Vanessa Jonsson (OH: M 3:30-4:30, Steele 3)
* Fiona Chandra (OH: W 4:30-5:30, Steele 3)
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=== 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.

===Announcements ===
* ODE and MATLAB Tutorial will be held Friday, Jan 7 at 1 pm in Steele 214
* 24 Oct 2010: web page creation

=== Textbook ===

The primary text for the course (available via the online bookstore) is
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| align=right | &nbsp;[Alon]&nbsp;
| U. Alon, ''An Introduction to Systems Biology: Design Principles of Biological Circuits'', CRC Press, 2006.
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The following additional texts and notes may be useful for some students:
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| align=right | &nbsp;[FBS]&nbsp;
| K. J. Astrom and R. M. Murray, ''Feedback Systems''.  Available online at http://www.cds.caltech.edu/~murray/amwiki.
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| align=right | &nbsp;[BFS]&nbsp;
| D. Del Vecchio and R. M. Murray, ''Biomolecular Feedback Systems''.  Available online at http://www.cds.caltech.edu/~murray/amwiki/BFS.
* Class version (Caltech access only): {{be250c pdf|wi11|caltech/bfs-class-frontmatter_16Jan11.pdf|TOC}}, {{be250c pdf|wi11|caltech/bfs-class-intro_01Jan11.pdf|Ch 1}}, {{be250c pdf|wi11|caltech/bfs-class-coreproc_01Jan11.pdf|Ch 2}},  {{be250c pdf|wi11|caltech/bfs-class-dynamics_16Jan11.pdf|Ch 3}}, {{be250c pdf|wi11|caltech/bfs-class-backmatter_16Jan11.pdf|Refs}}
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| align=right | &nbsp;[Klipp]&nbsp;
| Edda Klipp, Wolfram Liebermeister, Christoph Wierling, Axel Kowald, Hans Lehrach, Ralf Herwig, ''Systems biology: A textbook''.  Wiley, 2009.
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| align=right | &nbsp;[Strogatz]&nbsp;
| Steven Strogatz, ''Nonlinear Dynamics And Chaos: With Applications To Physics, Biology, Chemistry, And Engineering''.  Westview Press, 2001.
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SAMPLE MATLAB ODE FILES:
[http://www.its.caltech.edu/~fiona/be250c_TA/runfun.m runfun.m]
[http://www.its.caltech.edu/~fiona/be250c_TA/fun.m fun.m]

=== 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 ===
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| '''Week'''
| '''Date'''
| width=40% |  '''Topic'''
| width=40% | '''Reading'''
| '''Homework'''
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| 1 
| 4 Jan <br> 6 Jan <br><br> MBE
| Course overview; gene circuit dynamics
* Core processes in cells
* Modeling transcription, translation and regulation using ODEs
* Negative auto-regulation
Recitation sections (TAs):
* Ordinary differential equations
* [http://www.cds.caltech.edu/~vjonsson/bi250c2011/lectures/MATLABTutorial.pdf MATLAB tutorial ]
| 
* Alon, Ch 2: Transcription networks : basic concepts
* {{be250c pdf|wi11|caltech/bfs-class-coreproc_01Jan11.pdf|BFS, Ch 2}}: Modeling of Core Processes
* Alon, Ch 3: Autoregulation : a network motif
| <!-- Homework -->
[http://www.cds.caltech.edu/~vjonsson/bi250c2011/hw/hw1.pdf hw1]
[http://www.cds.caltech.edu/~murray/courses/bi-be250c/wi11/caltech/Hw1Sol.pdf Solutions]
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| 2
| 11 Jan <br> 13 Jan <br><br> MBE
| 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
| <!-- Homework -->
[http://www.cds.caltech.edu/~murray/wiki/images/5/5f/Hw-2.pdf HW2]
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| 3
| 18&nbsp;Jan <br> 20 Jan <br><br> 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
* [http://www.cds.caltech.edu/~murray/books/AM08/pdf/bfs09-L1_modeling_26Aug09.pdf Modeling of core processes]
* [http://www.cds.caltech.edu/~murray/courses/cds101/fa08/pdf/L2-1_stability_h.pdf Dynamics and stability in ODEs]
| 
* [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.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.
| <!-- Homework -->
[http://www.cds.caltech.edu/~murray/wiki/images/4/41/HW3_final.pdf HW3]
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| 4
| 25 Jan <br> 27 Jan <br><br> RMM
| Robustness
* Chemotaxis and perfect adaptation
* Controls analysis of robustness
|
* Alon, Ch 7: Robustness of protein circuits : the example of 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.
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| 5
| 1 Feb <br> 3 Feb <br><br> MBE
| Noise
* Random processes
* Intrinsic and extrinsic noise
* Stochastic modeling
Probabilistic differentiation (?)
| 
* 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.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.
| <!-- Homework -->
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| 6
| 8 Feb <br> 10 Feb <br><br> TAs
| Population dynamics and Evolution 
|
* [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2920833/  Computational Models of HIV-1 Resistance to Gene Therapy Elucidate Therapy Design Principles], Sharon Aviran, Priya S. Shah, David V. Schaffer, Adam P. Arkin.  ''PLoS Comput Biol.", 2010.


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| 7
| 15 Feb <br> 17 Feb <br><br> MBE
| Dynamic signal coding
* PWM
* FM
* NFkB example
| 
* [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/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
| <!-- Homework -->
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| 8
| 22 Feb <br> 24&nbsp;Feb <br><br> RMM
| Patterning
* Morphogenesis
* Robust morphagen gradient
* Proportionality and scaling
| 
* Alon, Ch 8: Robust Patterning in Development
* [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.
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| 9
| 1 Mar <br> 3 Mar <br><br> TBD
| Fine grain patterns
* Lateral inhibition
* Notch-delta
| <!-- Reading -->
| <!-- Homework -->
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| 10
| 8 Mar <br> <br> TBD
| Epistasis and modularity
* Flux balance analysis and yeast metabolism
* Antibiotic interactions
* Principle of monochroniticity (?)
| 
* [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.
| <!-- Homework -->

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