Systems Biology

Natural Sciences > Physics > Systems Biology

Systems Biology posted by member7_php on 2/12/2009

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Courseware/Lectures

Test/Tutorials

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.

Syllabus

Overview

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'

Text

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:

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

Calendar

LEC #	TOPICS	KEY DATES
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

Readings

MATLAB® software is required to run the .m files in this section.

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

Downloadable course notes are included courtesy of Prof. Alexander van Oudenaarden as well as any additional authors noted in the table below.
LEC #	TOPICS	READINGS
Part I: Systems Microbiology - 'The Cell as a Well-stirred Bioreactor'
1	Introduction Michaelis-Menten Kinetics
2	Equilibrium Binding Cooperativity	Michaelis-Menten Kinetics Associated MATLAB® code file (M)
3	Lambda Phage Multistability	A Genetic Switch in Lamba Phage 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 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
7	Introduction E. coli Chemotaxis
8	Fine-tuned versus Robust Chemotaxis Models	Modeling Escherichia coli chemotaxis 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
10	Genetic Oscillators	Biological Oscillators 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 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 (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
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 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.