Systems Biology

Readings

To facilitate interactions during class between students, there are short required questions about the reading that will be due before class.

Required Texts

[UA] = Alon, U. An Introduction to Systems Biology: Design Principles of Biological Circuits. Chapman and Hall / CRC, 2006. ISBN: 9781584886426. [Preview with Google Books]

[MN] = Nowak, M. A. Evolutionary Dynamics: Exploring the Equations of Life. Belknap Press, 2006. ISBN: 9780674023383. [Preview with Google Books]

Supplementary Reading

[BA] = Alberts, B., et al. Essential Cell Biology. 3rd ed. Garland Science, 2009. ISBN: 9780815341291.

[SS] = Strogatz, Steven H. Nonlinear Dynamics and Chaos: With Applications to Physics, Biology, Chemistry, and Engineering. Westview Press, 2014. ISBN: 9780813349107. [Preview with Google Books]

SES #	TOPICS	READINGS
1	Introduction to the class and overview of topics. Basic concepts in networks and chemical reactions.	Optional [BA] Chapter 1.
2	Input function of a gene, Michaelis-Menten kinetics, and cooperativity	Required [UA] Chapters 1 and 2. [UA] Appendix A. Optional [BA] Chapter 3, pp. 98–103. [BA] Chapter 7: “From DNA to Protein: How Cells Read the Genome.”  [BA] Chapter 8, pp. 269–80.
3	Autoregulation, feedback and bistability	Required [UA] Chapter 3. Optional [SS] Chapters 1 and 2. Becskei, A., and L. Serrano. “Engineering Stability in Gene Networks by Autoregulation.” Nature 405 (2000): 590–3.
4	Introduction to synthetic biology and stability analysis in the toggle switch	Required Hasty, J., D. McMillen, et al. “Engineered Gene Circuits.” Nature 420 (2002): 224–30. Supplementary notes on Stability Analysis (PDF) written by Alexander van Oudenaarden. Optional [SS] Chapters 5 and 6. Gardner, T. S., C. R. Cantor, et al. “Construction of a Genetic Toggle Switch in Escherichia Coli.” Nature 403 (2000): 339–42.
5	Oscillatory genetic networks	Required Elowitz, M. B., and S. Leibler. “A Synthetic Oscillatory Network of Transcriptional Regulators.” Nature 403 (2000): 335–38. Optional [SS] Chapter 7. Stricker, J., S. Cookson, et al. “A Fast, Robust and Tunable Synthetic Gene Oscillator.” Nature 456 (2008): 516–19.
6	Graph properties of transcription networks	Required [UA] Appendix C. [UA] Chapters 4.1–4.3 Barabasi, A. L., and R. Alpert. “Emergence of Scaling in Random Networks.” Science 286, no. 5439 (1999): 509–12.
7	Feed-forward loop network motif	Required [UA] Chapter 4.
8	Introduction to stochastic gene expression	Required [UA] Appendix D. Yu, J., J. Xiao, et al. “Probing Gene Expression in Live Cells, One Protein Molecule at a Time.” Science 311, no. 5767 (2006): 1600–3.
9	Causes and consequences of stochastic gene expression	Required Raj, A., and A. van Oudenaarden. “Nature, Nurture, or Chance: Stochastic Gene Expression and Its Consequences.” Cell 135, no. 2 (2008): 216–26. Optional Elowitz, M. B., A. J. Levine, et al. “Stochastic Gene Expression in a Single Cell.” Science 297, no. 5584 (2002): 1183–86.
10	Stochastic modeling—The master equation, Fokker-Planck Equation, and the Gillespie algorithm	Required Supplementary notes on the Master Equation and Fokker Plank Equation (PDF), by Alexander van Oudenaarden. Optional Gillespie, D. T. “Exact Stochastic Simulation of Coupled Chemical Reactions.” The Journal of Physical Chemistry 81, no. 25 (1977): 2340–61.
11	Life at low Reynold’s number	Required Purcell, E. M. “Life at Low Reynolds Number.” American Journal of Physics 45, no. 3 (1977): 3–11. Optional Berg, H. C., and E. M. Purcell. “Physics of Chemoreception.” Biophysical Journal 20, no. 2 (1977): 193–219.
12	Robustness and bacterial chemotaxis	Required [UA] Chapter 7. Optional Barkai, N., and S. Leibler. “Robustness in Simple Biochemical Networks.” Nature 387, no. 6636 (1997): 913–17. Alon, U., M. G. Surette, et al. “Robustness in Bacterial Chemotaxis.” Nature 397 (1999): 168–71.
13	Robustness in development and pattern formation	Required [UA] Chapter 8. Supplementary notes on Fick’s Law (PDF) by Alexander van Oudenaarden. Kondo, S., and T. Miura. “Reaction-Diffusion Model as a Framework for Understanding Biological Pattern Formation.” Science 329, no. 5999 (2010): 1616–20. Optional Loose, M., E. Fischer-Friedrich, et al. “Spatial Regulators for Bacterial Cell Division Self Organize into Surface Waves in Vitro.” Science 320, no. 5877 (2008): 789–92.
14	Introduction to microbial evolution experiments, and optimal gene circuit design	Required [MN] Chapters 1–2. Dekel, E., and U. Alon. “Optimality and Evolutionary Tuning in the Expression Level of a Protein.” Nature 436 (2005): 588–92. Optional [UA] Chapter 10. Elena, S. F., and R. E. Lenski. “Evolution Experiments with Micro-organisms: The Dynamics and Genetic Bases of Adaptation.” Nature Reviews Genetics 4 (2003): 457–69.
15	Evolution in finite populations, genetic drift, and the theory of neutral molecular evolution	Required Duret, L. “Neutral Theory: The Null Hypothesis of Molecular Evolution.” Nature Education 1, no. 1 (2008). [MN] Chapter 6.
16	Clonal interference and the distribution of beneficial mutations	Required Hegreness, M., N. Shoresh, et al. “An Equivalence Principle for the Incorporation of Favorable Mutations in Asexual Populations.” Science 311, no. 5767 (2006): 1615–17. Optional Orr, H. A. “The Genetic Theory of Adaptation: A Brief History.” Nature Reviews Genetics 6 (2005): 119–27. Desai, M., D. S. Fisher, et al. “The Speed of Evolution and Maintenance of Variation in Asexual Populations.” Current Biology 17, no. 5 (2007): 385–94. Weissman, D. B., M. M. Desai, et al. “The Rate at which Asexual Populations Cross Fitness Valleys.” Theoretical Population Biology 75, no. 4 (2009): 286–300.
17	Fitness landscapes and sequence spaces	Required [MN] Chapter 3. Weinreich, D. M., N. F. Delaney, et al. “Darwinian Evolution Can Follow Only Very Few Mutational Paths to Fitter Proteins.” Science 312, no. 5770 (2006): 111–4.
18	Evolutionary games	Required [MN] Chapter 4. Optional Turner, P. E., and L. Chao. “Prisoner’s Dilemma in an RNA Virus.” Nature 398 (1999): 441–43.
19	Survival in fluctuating environments	Required Mitchell, A., G. H. Romano, et al. “Adaptive Prediction of Environmental Change by Micro-Organisms.” Nature 460 (2009): 220–24. Kussell, E., and S Leibler. “Phenotypic Diversity, Population Growth, and Information in Fluctuating Environments.” Science 309, no. 5743 (2005): 2075–78.
20	Parasites, the evolution of virulence and sex	Required [MN] Chapter 11. Morran, L., O. Schmidt, et al. “Running with the Red Queen: Host-Parasite Coevolution Selects for Biparental Sex.” Science 333, no. 6039 (2011): 216–18. Optional Lloyd-Smith, J. O., S. J. Schreiber, et al. “Superspreading and the Effect of Individual Variation on Disease Emergence.” Nature 438 (2005): 355–59.
21	Interspecies interactions, the Lotka-Volterra model, and predator-prey oscillations	Required Edelstein-Keshet, L. Sections 6.2, 6.6, and 6.7 in Mathematical Models in Biology. Society for Industrial and Applied Mathematics, 2005. ISBN: 9780898715545. Yoshida, T., L. E. Jones, et al. “Rapid Evolution Drives Ecological Dynamics in a Predator-prey System.” Nature 424 (2003): 303–06. Optional McKane, A. J., and T. J. Newman. “Predator-Prey Cycles from Resonant Amplification of Demographic Stochasticity.” Physical Review Letters 94 (2010): 218102.
22	Ecosystem stability, critical transitions, and the maintenance of biodiversity	Required Scheffer, M., J. Bascompte, et al. “Early-warning Signals for Critical Transitions.” Nature 461 (2009): 53–59. Optional [SS] Chapter 3. Dai, L., D. Vorselen, et al. “Generic Indicators for Loss of Resilience Before a Tipping Point Leading to Population Collapse.” Science 336, no. 6085 (2012): 1175–77.
23	Dynamics of populations in space	Required Hallatschek, O., and D. R. Nelson. “Population Genetics and Range Expansions.” Physics Today 62, no. 7 (2009): 42. Kerr, B., M. A. Riley, et al. “Local Dispersal Promotes Biodiversity in a Real-Life Game of Rock-Paper-Scissors.” Nature 418, no. 6894 (2002): 171–74.
24	The neutral theory of ecology	Required Whitfield, J. “Ecology: Neutrality Versus the Niche.” Nature 417 (2002): 480–81. Volkov, I., J. Banavar, et al. “Neutral Theory and Relative Species Abundance in Ecology.” Nature 424 (2003): 1035–37.