8.591J | Fall 2004 | Graduate

Systems Biology


Suggested Readings in Biology

The following sections from Alberts, Bruce, et al. Molecular Biology of the Cell. 4th ed. New York: Garland Science, 2002. ISBN: 9780815332183, are suggested:

  • RNA and Protein Synthesis
  • Overview of Gene Control
  • How Genetic Switches Work
  • General Principles of Cell Signaling

Part I: Systems Microbiology - ‘The Cell as a Well-stirred Bioreactor’
1 Introduction

Michaelis-Menten Kinetics

2 Equilibrium Binding


Michaelis-Menten Kinetics (PDF)

Associated MATLAB® code file (M)

3 Lambda Phage


A Genetic Switch in Lamba Phage (PDF)

Associated MATLAB® code file (M)

Hasty, Jeff, Joel Pradines, Milos Dolnik, and J. J. Collins. “Noise-based Switches and Amplifiers for Gene Expression.” Proc. Natl. Acad. Sci. USA 97, no. 5 (Feb 29, 2000): 2075-80.

4 Multistability (cont.) Isaacs, Farren J., Jeff Hasty, Charles R. Cantor, and J. J. Collins. “Prediction and Measurement of an Autoregulatory Genetic Module.” PNAS 100, no. 13 (June 24, 2003): 7714-19.
5 Synthetic Genetic Switches Synthetic Genetic Switches (PDF)

Gardner, Timothy S., Charles R. Cantor, and James J. Collins. “Construction of a Genetic Toggle Switch in Escherichia coli.” Nature 403, no. 6767 (January 20, 2000): 339-42.

6 Stability Analysis Stability Analysis (PDF)
7 Introduction E. coli Chemotaxis  
8 Fine-tuned versus Robust Chemotaxis Models Modeling Escherichia coli chemotaxis (PDF)

Associated MATLAB® code file (M)

Spiro, Peter A., John S. Parkinson, and Hans G. Othmer. “A Model of Excitation and Adaptation in Bacterial Chemotaxis.” Proc. Natl. Acad. Sci. USA 94, no. 14 (July, 1997): 7263–68.

9 Wrapping up Chemotaxis Biological Oscillators (PDF)
10 Genetic Oscillators Biological Oscillators (PDF)

Associated MATLAB® code file (M)

Elowitz, Michael B., and Stanislas Leibler. “A Synthetic Oscillatory Network of Transcriptional Regulators.” Nature 403, no. 6767 (January 20, 2000): 335-8.

11 Genetic Oscillators (cont.) Routh-Hurwitz (PDF)

Associated MATLAB® code file (M)

Atkinson, Mariette R., Michael A. Savageau, Jesse T. Myers, and Alexander J. Ninfa. “Development of Genetic Circuitry Exhibiting Toggle Switch or Oscillatory Behavior in Escherichia coli.” Cell 113, no. 5 (May 30, 2003): 597-607.

12 Stochastic Chemical Kinetics The Origin and Consequences of Noise in Biochemical Systems (PDF) (Courtesy of Alexander van Oudenaarden and Mukund Thattai. Used with permission.)
13 Stochastic Chemical Kinetics (cont.)  
Part II: Cell Systems Biology - ‘The Importance of Diffusion and Gradients for Cellular Regulation’
14 Introduction Cell Systems Biology

Fick’s Laws

15 Local Excitation

Global Inhibition Theory

Local Excitation, Global Inhibition Model (PDF)
16 Local Excitation (cont.)

Global Inhibition Theory (cont.)

17 Rapid Pole-to-pole Oscillations in E. coli Howard, Martin, Andrew D. Rutenberg, and Simon de Vet. “Dynamic Compartmentalization of Bacteria: Accurate Division in E. Coli.Physical Review Letters 87, no. 27 (December 31, 2001).
18 Rapid Pole-to-pole Oscillations in E. coli (cont.)  
19 Models for Eukaryotic Gradient Sensing Models for Eukaryotic Gradient Sensing (PDF)

Associated MATLAB® code file (M)

Narang, Atul, K. K. Subramanian, and D. A. Lauffenburger. “A Mathematical Model for Chemoattractant Gradient Sensing based on Receptor-regulated Membrane Phospholipid Signaling Dynamics.” Annals of Biomedical Engineering 29, no. 8 (2001): 677-91.

20 Models for Eukaryotic Gradient Sensing (cont.) Postma, Marten, and Peter J. M. Van Haastert. “A Diffusion–Translocation Model for Gradient Sensing by Chemotactic Cells.” Biophysical Journal 81, no. 3 (September, 2001): 1314-23.
21 Modeling Cytoskeleton Dynamics Dogterom, Marileen, and Stanislas Leibler. “Physical Aspects of the Growth and Regulation of Microtubule Structures.” Physical Review Letters 70, no. 9 (March 1, 1993).
22 Modeling Cytoskeleton Dynamics (cont.) Cytrynbaum, E. N., V. Rodionov, and A. Mogilner. “Computational Model of Dynein-dependent Self-organization of Microtubule Asters.” Journal of Cell Science 117, no. 8 (March 15, 2004): 1381-97.
Part III: Developmental Systems Biology - ‘Building an Organism Starting From a Single Cell’
23 Quorum Sensing You, Lingchong, Robert Sidney Cox III, Ron Weiss, and Frances H. Arnold. “Programmed Population Control by Cell-Cell Communication and Regulated Killing.” Nature 428, no. 6985 (April 22, 2004): 868-71.
24 Final Problem Set Question Hour  
25 Drosophila Development Houchmandzadeh, Bahram, Eric Wieschaus, and Stanislas Leibler. “Establishment of Developmental Precision and Proportions in the Early Drosophila embryo.” Nature 415, no. 6873 (February 14, 2002): 798-802.

Course Info

As Taught In
Fall 2004
Learning Resource Types
Lecture Notes
Problem Sets