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van Oudenaarden, Alexander, 8.591J Systems Biology, Fall 2004. (Massachusetts Institute of Technology: MIT OpenCourseWare), (Accessed 09 Jul, 2010). License: Creative Commons BY-NC-SA

Fall 2004

Diagram of the chemotactic pathway in E. coli. (Figure by MIT OCW. After figure 4 in Falke, J. J., R. B. Bass, S. L. Butler, S. A. Chervitz, and M. A. Danielson. "The Two-component Signaling Pathway of Bacterial Chemotaxis: A Molecular View of Signal Transduction by Receptors, Kinases, and Adaptation Enzymes." In Annu Rev Cell Dev Biol. 13 (1997): 457-512.)

Course Highlights

This course features a set of course notes in the readings section.

Course Description

This course introduces the mathematical modeling techniques needed to address key questions in modern biology. An overview of modeling techniques in molecular biology and genetics, cell biology and developmental biology is covered. Key experiments that validate mathematical models are also discussed, as well as molecular, cellular, and developmental systems biology, bacterial chemotaxis, genetic oscillators, control theory and genetic networks, and gradient sensing systems. Additional specific topics include: constructing and modeling of genetic networks, lambda phage as a genetic switch, synthetic genetic switches, circadian rhythms, reaction diffusion equations, local activation and global inhibition models, center finding networks, general pattern formation models, modeling cell-cell communication, quorum sensing, and finally, models for Drosophila development.

Technical Requirements

MATLAB® software is required to run the .m files found on this course site.



The goal of this course is to help students develop a quantitative understanding of the biological function of genetic and biochemical networks. Students will be provided with the essential mathematical tools needed to model network modules, such as biological switches, oscillators, filters, amplifiers, etc. An array of example biological problems that can be successfully tackled with a systems biology approach will be introduced by discussing recent papers on the subject. The intrinsic challenge of this class is that students are coming in with wildly different backgrounds. Read up on your biology or math if needed. Use time in the recitations to help close some of the knowledge gaps and to help you prepare for the homework.

There are three levels of complexity to Systems Biology:

  • I Systems Microbiology (14 Lectures) 'The cell as a well-stirred biochemical reactor'
  • II Systems Cell Biology (8 Lectures) 'The cell as a compartmentalized system with concentration gradients'
  • III Systems Developmental Biology (3 Lectures) 'The cell in a social context communicating with neighboring cells'


The course notes serve as the text. For good biology reference texts, see:

Alberts, Bruce, et. al. Molecular Biology of the Cell. 4th ed. New York: Garland Science, 2002. ISBN: 9780815332183.

Lodish, Harvey, et al. Molecular Cell Biology. 5th ed. New York: W. H. Freeman and Company, 2003. ISBN: 9780716743668.

Assignments, Exams, and Grading

MATLAB® will be used intensively during the course. Make sure you know or learn how to use it as it is necessary for the problem sets.

There are 5 problem sets and one take home final for the course. The grading breakdown is as follows:

Problem set 1 15%
Problem set 2 15%
Problem set 3 15%
Problem set 4 15%
Problem set 5 15%
Final 25%


Part I: Systems Microbiology - 'The Cell as a Well-stirred Bioreactor'
1 Introduction Michaelis-Menten Kinetics  
2 Equilibrium Binding Cooperativity  
3 Lambda Phage Multistability  
4 Multistability (cont.)  
5 Synthetic Genetic Switches  
6 Stability Analysis  
7 Introduction E. coli Chemotaxis  
8 Fine-tuned versus Robust Chemotaxis Models Problem set 1 due
9 Wrapping up Chemotaxis  
10 Genetic Oscillators  
11 Genetic Oscillators (cont.)  
12 Stochastic Chemical Kinetics Problem set 2 due
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  
16 Local Excitation (cont.) Global Inhibition Theory (cont.) Problem set 3 due
17 Rapid Pole-to-pole Oscillations in E. coli  
18 Rapid Pole-to-pole Oscillations in E. coli (cont.)  
19 Models for Eukaryotic Gradient Sensing Problem set 4 due
20 Models for Eukaryotic Gradient Sensing (cont.)  
21 Modeling Cytoskeleton Dynamics  
22 Modeling Cytoskeleton Dynamics (cont.) Problem set 5 due
Part III: Developmental Systems Biology - 'Building an Organism Starting From a Single Cell'
23 Quorum Sensing  
24 Final Problem Set Question Hour  
25 Drosophila Development Take home final due   Tell A Friend