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8.591

Systems Biology

3-0-9 units · Graduate

Introduction to cellular and population-level systems biology with an emphasis on synthetic biology, modeling of genetic networks, cell-cell interactions, and evolutionary dynamics. Cellular systems include genetic switches and oscillators, network motifs, genetic network evolution, and cellular decision-making. Population-level systems include models of pattern formation, cell-cell communication, and evolutionary systems biology. Students taking graduate version explore the subject in more depth.

Fall 2014

This course provides an introduction to cellular and population-level systems biology with an emphasis on synthetic biology, modeling of genetic networks, cell-cell interactions, and evolutionary dynamics. Cellular systems include genetic switches and oscillators, network motifs, genetic network evolution, and cellular decision-making. Population-level systems include models of pattern formation, cell-cell communication, and evolutionary systems biology.

Readings

Fall 2004

Topics

  • Introduction
  • Equilibrium Binding
  • Lambda Phage
  • Multistability (cont.)
  • Synthetic Genetic Switches
  • Stability Analysis
  • Introduction E. coli Chemotaxis
  • Fine-tuned versus Robust Chemotaxis Models
  • Wrapping up Chemotaxis
  • Genetic Oscillators
  • Genetic Oscillators (cont.)
  • Stochastic Chemical Kinetics
  • Stochastic Chemical Kinetics (cont.)
  • Introduction Cell Systems Biology
  • Local Excitation
  • Local Excitation (cont.)
  • Rapid Pole-to-pole Oscillations in E. coli
  • Rapid Pole-to-pole Oscillations in E. coli (cont.)
  • Models for Eukaryotic Gradient Sensing
  • Models for Eukaryotic Gradient Sensing (cont.)
  • Modeling Cytoskeleton Dynamics
  • Modeling Cytoskeleton Dynamics (cont.)
  • Quorum Sensing
  • Final Problem Set Question Hour
  • Drosophila Development

Readings

  • The following sections from Alberts, Bruce, et al. Molecular Biology of the Cell. 4th ed. New York: Garland Science, 2002. ISBN: 9780815332183, are suggested:
    Listed reading
  • 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.
    Listed reading
  • LEC #: 4 · TOPICS: Multistability (cont.) · READINGS: 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.
    Reading assignment
  • Reading assignment
  • 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.
    Listed reading
  • Reading assignment
  • Reading assignment
  • 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.
    Listed reading
  • Reading assignment
  • Reading assignment
  • Elowitz, Michael B., and Stanislas Leibler. “A Synthetic Oscillatory Network of Transcriptional Regulators.” Nature 403, no. 6767 (January 20, 2000): 335-8.
    Listed reading
  • Reading assignment
  • 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.
    Listed reading
  • Reading assignment
  • LEC #: 17 · TOPICS: Rapid Pole-to-pole Oscillations in E. coli · READINGS: 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).
    Reading assignment
  • Reading assignment
  • 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.
    Listed reading
  • LEC #: 20 · TOPICS: Models for Eukaryotic Gradient Sensing (cont.) · READINGS: 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.
    Reading assignment
  • LEC #: 21 · TOPICS: Modeling Cytoskeleton Dynamics · READINGS: Dogterom, Marileen, and Stanislas Leibler. “Physical Aspects of the Growth and Regulation of Microtubule Structures.” Physical Review Letters 70, no. 9 (March 1, 1993).
    Reading assignment
  • LEC #: 22 · TOPICS: Modeling Cytoskeleton Dynamics (cont.) · READINGS: 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.
    Reading assignment
  • LEC #: 23 · TOPICS: Quorum Sensing · READINGS: 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.
    Reading assignment
  • LEC #: 25 · TOPICS: Drosophila Development · READINGS: 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.
    Reading assignment
  • Alberts, Bruce, et. al. Molecular Biology of the Cell . 4th ed. New York: Garland Science, 2002. ISBN: 9780815332183.
    Listed reading
  • Lodish, Harvey, et al. Molecular Cell Biology . 5th ed. New York: W. H. Freeman and Company, 2003. ISBN: 9780716743668.
    Listed reading

Prerequisites & course information

Same subject as 7.81[J] Subject meets with 7.32 Prereq: ( 18.03 and 18.05 ) or permission of instructor G (Fall) 3-0-9 units

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