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

Required Texts

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

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

Supplementary Reading

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

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

1 Introduction to the class and overview of topics. Basic concepts in networks and chemical reactions.


[BA] Chapter 1.

2 Input function of a gene, Michaelis-Menten kinetics, and cooperativity


[UA] Chapters 1 and 2.

[UA] Appendix A.


[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


[UA] Chapter 3.


[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


Hasty, J., D. McMillen, et al. "Engineered Gene Circuits." Nature 420 (2002): 224–30.

Supplementary notes on This resource may not render correctly in a screen reader.Stability Analysis (PDF) written by Alexander van Oudenaarden.


[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


Elowitz, M. B., and S. Leibler. "A Synthetic Oscillatory Network of Transcriptional Regulators." Nature 403 (2000): 335–38.


[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


[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


[UA] Chapter 4.

8 Introduction to stochastic gene expression


[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


Raj, A., and A. van Oudenaarden. "Nature, Nurture, or Chance: Stochastic Gene Expression and Its Consequences." Cell 135, no. 2 (2008): 216–26.


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


Supplementary notes on the This resource may not render correctly in a screen reader.Master Equation and Fokker Plank Equation (PDF), by Alexander van Oudenaarden.


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


Purcell, E. M. "Life at Low Reynolds Number." American Journal of Physics 45, no. 3 (1977): 3–11.


Berg, H. C., and E. M. Purcell. "Physics of Chemoreception." Biophysical Journal 20, no. 2 (1977): 193–219.

12 Robustness and bacterial chemotaxis


[UA] Chapter 7.


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


[UA] Chapter 8.

Supplementary notes on This resource may not render correctly in a screen reader.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.


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


[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.


[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


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


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.


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


[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


[MN] Chapter 4.


Turner, P. E., and L. Chao. "Prisoner's Dilemma in an RNA Virus." Nature 398 (1999): 441–43.

19 Survival in fluctuating environments


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


[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.


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


Buy at Amazon 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.


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


Scheffer, M., J. Bascompte, et al. "Early-warning Signals for Critical Transitions." Nature 461 (2009): 53–59.


[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


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


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.