View source for BE 150/Bi 250b Winter 2012

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<font color='blue' size='+2'>Systems Biology</font>__NOTOC__
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'''Instructors'''
* Michael Elowitz (Bi/BE/APh)
* Richard Murray (CDS/BE)
* Lectures: MW 10-11, 101 Kerckhoff
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'''Teaching Assistants'''
* Emzo de los Santos
* Vanessa Jonsson
* Recitation: F 10-11, 111 Keck (BE 150), 3 BBB (Bi 250)
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=== Lecture Schedule ===
There will be two 1-hour lectures each week, as well as a 1-hour recitation section.
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| '''Week'''
| '''Date'''
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| width=40% | '''Reading'''
| '''Homework'''
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===== 1 =====
| 4 Jan <br> 6 Jan+ <br> MBE/RMM
| Course overview
* Principles in systems biology
Recitation section:
* MATLAB tutorial (optional)
[https://www.cds.caltech.edu/~murray/wiki/images/6/64/MatlabTutorial.pdf  Matlab Tutorial]
| 
Bi 250b:
* Alon, Ch 1: Introduction

BE 150:
* {{be150 pdf|wi12|caltech/bfs-class-intro_01Jan12.pdf|BFS, Ch 1}}: Introductory Concepts
* {{be150 pdf|wi12|caltech/bfs-class-coreproc_18Jan12.pdf|BFS, Ch 2}}: Modeling of Core Processes
** Section 2.1: Modeling Techniques
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===== 2 =====
| 9 Jan <br> 11 Jan+ <br><br> MBE
| Gene circuit dynamics
* Core processes in cells
* Modeling transcription, translation and regulation using ODEs
* Negative auto-regulation
| 
Bi 250b:
* Alon, Ch 2: Transcription networks : basic concepts
* Alon, Ch 3: Autoregulation : a network motif

BE 150:
* {{be150 pdf|wi12|caltech/bfs-class-coreproc_18Jan12.pdf|BFS, Ch 2}}: Modeling of Core Processes
** Sections 2.2-2.3: transcription and translation, transcriptional regulation

Papers discussed in lecture:
* [http://www.nature.com/nature/journal/v403/n6767/abs/403339a0.html Construction of a genetic toggle switch in <i>Escherichia coli </i>], Gardner TS, Cantor CR, Collins JJ. ''Nature'', <b>403</b>:339-342, 2000.
* [http://www.nature.com/nature/journal/v426/n6965/abs/nature02089.html A positive-feedback-based bistable 'memory module' that governs a cell fate decision], Xiong and Ferrell. ''Nature'', <b>426</b>:460-465, 2003.
|[https://www.cds.caltech.edu/~murray/wiki/images/c/c6/Hw1.pdf BEHW1] [https://www.cds.caltech.edu/~murray/wiki/images/e/e1/Hw1bio.pdf BIOHW1]
* [http://www.cds.caltech.edu/~murray/courses/be150/wi12/lacIOpenMain.m lacIOpenMain.m]
* [http://www.cds.caltech.edu/~murray/courses/be150/wi12/lacIClosedMain.m lacIClosedMain.m]
* [http://www.cds.caltech.edu/~murray/courses/be150/wi12/lacIOpen.m lacIOpen.m]
* [http://www.cds.caltech.edu/~murray/courses/be150/wi12/lacIClosed.m lacIClosed.m]
* [http://www.cds.caltech.edu/~murray/courses/be150/wi12/toggleMain.m toggleMain.m]
* [http://www.cds.caltech.edu/~murray/courses/be150/wi12/toggle.m toggle.m]
* [http://www.cds.caltech.edu/~murray/courses/be150/wi12/posFeedMain.m posFeedMain.m]
* [http://www.cds.caltech.edu/~murray/courses/be150/wi12/posFeed.m posFeed.m]
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===== 3 =====
| <s>16 Jan</s> <br> 18 Jan* <br> 20 Jan* <br><br> RMM
| Circuit motifs
* Feedforward loops (FFLs)
* Phosphorylation cascades
* Two-component signaling systems
* Sequestration for ultrasensitivty
| 
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:
* {{be250c pdf|wi12|caltech/bfs-class-coreproc_18Jan21.pdf|BFS, Ch 2}}: Modeling of Core Processes
** Section 2.4: post-transcriptoinal regulation
** Section 2.5: cellular subsystems

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.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.
| [https://www.cds.caltech.edu/~murray/wiki/images/7/74/Hw2.pdf BEHW2] [https://www.cds.caltech.edu/~murray/wiki/images/5/51/Hw2_bio.pdf BIOHW2]
* [http://www.cds.caltech.edu/~murray/courses/be150/wi12/prob1.m prob1.m]
* [http://www.cds.caltech.edu/~murray/courses/be150/wi12/plot1.m plot1.m]
* [http://www.cds.caltech.edu/~murray/courses/be150/wi12/phosphoMainIO.m phosphoMainIO.m]
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===== 4 =====
| 23&nbsp;Jan <br> 25 Jan <br><br> MBE
| Biological clocks: how to produce oscillations in cells
* Plant clocks/circadian rhythm
* Synthetic oscillators (repressilator, dual-feedback oscillator)
* Circadian clocks in cyanobacteria
| 
* [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.
BE 150:
* {{be150 pdf|wi12|caltech/bfs-class-dynamics_18Jan12.pdf|BFS, Ch 3}}: Analysis of Dynamic Behavior
** Sections 3.5: Oscillatory Behavior
|[https://www.cds.caltech.edu/~murray/wiki/images/4/4b/Hw3.pdf BEHW3] [https://www.cds.caltech.edu/~murray/wiki/images/e/e1/Hw3bio.pdf BIOHW3]
* [http://www.cds.caltech.edu/~murray/courses/be150/wi12/ddeoscillate.m  ddeoscillate.m] 
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===== 5 =====
| 30 Jan <br> 1 Feb <br><br> RMM
| Robustness
* Chemotaxis and perfect adaptation
* Fold change detection
* Controls analysis of robustness
|
* Alon, Ch 7: Robustness of protein circuits : the example of bacterial chemotaxis
* 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.
* (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 pdf|wi12|caltech/bfs-class-dynamics_29Jan12.pdf|BFS, Ch 3}}: Sec 3.3 (Robustness) and Sec 3.6 (Bifurcations)
* {{be150 pdf|wi12|caltech/bfs-class-chemotaxis_29Jan12.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.
| [https://www.cds.caltech.edu/~murray/wiki/images/d/d3/Be150hw4.pdf BE150 HW #4] [https://www.cds.caltech.edu/~murray/wiki/images/8/88/Bi250bHw4.pdf Bi250b HW#4]
*[http://www.cds.caltech.edu/~murray/courses/be150/wi12/problem1.nb problem1.nb]
*[http://www.cds.caltech.edu/~murray/courses/be150/wi12/chemotaxis.m chemotaxis.m]
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===== 6 =====
| 6 Feb* <br> 8 Feb <br><br> RMM
| Noise
* Random processes
* Intrinsic and extrinsic noise
* Stochastic modeling: master equation, SSA
| 
* 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.
BE 150:
* {{be150 pdf|wi12|caltech/bfs-class-stochastic_29Jan12.pdf|BFS, Ch 4}}: Stochastic behavior
* {{be150 pdf|wi12|caltech/bfs-class-random_29Jan12.pdf|BFS, App C}}: Probability and random processes (optional)

| 
[https://www.cds.caltech.edu/~murray/wiki/images/6/68/Hw5-be.pdf  BEHW5]  [https://www.cds.caltech.edu/~murray/wiki/images/a/a7/Hw5-bio.pdf BIOHW5] 
* [http://www.cds.caltech.edu/~murray/courses/be150/wi12/runner.m runner.m]
* [http://www.cds.caltech.edu/~murray/courses/be150/wi12/hw5.sbproj hw5.sbproj]
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===== 7 =====
| 13 Feb+ <br> 15 Feb <br><br> MBE
| Burstiness in gene expression and signalling
* Birth-death processes
| 
* [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
| [https://www.cds.caltech.edu/~murray/wiki/images/7/75/Hw6-be.pdf BEHW6] [https://www.cds.caltech.edu/~murray/wiki/images/f/fe/Hw6-bio.pdf BIOHW6]
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===== 8 =====
| <s>20 Feb</s> <br> 22&nbsp;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.
| [https://www.cds.caltech.edu/~murray/wiki/images/d/df/Hw7-be.pdf BEHW7] [https://www.cds.caltech.edu/~murray/wiki/images/d/d5/Hw7-bio.pdf BioHW7] 
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===== 9 =====
| 27 Feb <br> 29 Feb*+ <br><br> MBK
| Modeling of complex biological networks (Mary Kennedy)
| 
* [http://www.ncbi.nlm.nih.gov/pubmed/20168991 A Dynamic Model of Interactions of Ca2+, Calmodulin, and Catalytic Subunits of Ca2+/Calmodulin-Dependent Protein Kinase II].  Pepke, S., Kinzer-Ursem, T., Mihalas, S., and Kennedy, M.B. (2010). PLoS Comput Biol 6, e1000675.  
* [http://www.ncbi.nlm.nih.gov/pubmed/20151023 Fast Monte Carlo simulation methods for biological reaction-diffusion systems in solution and on surfaces].  Kerr, R.A., Bartol, T.M., Kaminsky, B., Dittrich, M., Chang, J.-C.J., Baden, S.B., Sejnowski, T.J., and Stiles, J.R. (2008).  SIAM Journal on Scientific Computing 30, 3126-3149.   
* [http://www.ncbi.nlm.nih.gov/pubmed/12447978 Complexity of calcium signaling in synaptic spines]. Franks, K.M., and Sejnowski, T.J. (2002). Bioessays 24, 1130-1144.  
| <!-- Homework -->
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===== 10 =====
| 5  Mar <br> 7 Mar+ <br> MBE
| Fine grain patterns
* Lateral inhibition
* Notch-delta
| 
* [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
| [https://www.cds.caltech.edu/~murray/wiki/images/d/d6/Hw8-be.pdf BEHW8] [https://www.cds.caltech.edu/~murray/wiki/images/e/ef/Hw8-bio.pdf BioHW8] 
* [http://www.cds.caltech.edu/~murray/courses/be150/wi12/NotchDeltaGui.m NotchDeltaGui.m]
|}
<br>

=== 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
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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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Students in BE 150 should also obtain the following notes (freely downloadable from the web):
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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.
* Note: these notes are being written and will be updated during the course
* Class version (Caltech access only, 29 Jan 2012): {{be150 pdf|wi12|caltech/bfs-class-frontmatter_01Jan12.pdf|TOC}}, {{be150 pdf|wi12|caltech/bfs-class-intro_01Jan12.pdf|Ch 1}}, {{be150 pdf|wi12|caltech/bfs-class-coreproc_18Jan12.pdf|Ch 2}},  {{be150 pdf|wi12|caltech/bfs-class-dynamics_29Jan12.pdf|Ch 3}},  {{be150 pdf|wi12|caltech/bfs-class-stochastic_29Jan12.pdf|Ch 4}}, {{be150 pdf|wi12|caltech/bfs-class-chemotaxis_29Jan12.pdf|Sec 5.2}}, {{be150 pdf|wi12|caltech/bfs-class-random_29Jan12.pdf|App C}}, {{be150 pdf|wi12|caltech/bfs-class-backmatter_01Jan12.pdf|Refs}}
|}

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;[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.
|}

=== 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.



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