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Robustness, stability and efficiency of phage lambda genetic switch: dynamical structure analysis.

X-M Zhu1, L Yin, L Hood

  • 1GenMath, Corp. 5525 27th Ave.N.E., Seattle, WA 98105, USA.

Journal of Bioinformatics and Computational Biology
|December 24, 2004
PubMed
Summary
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This study presents a mathematical framework for the phage lambda genetic switch, explaining its stability and robustness through dynamical structure theory and stochastic effects. The model accurately predicts experimental observations for phage lambda.

Area of Science:

  • Systems Biology
  • Molecular Biology
  • Theoretical Biology

Background:

  • The phage lambda life cycle is controlled by a genetic switch.
  • Previous models by Shea and Ackers (1980s) described gene regulation.
  • Dynamical structure theory provides a framework for complex networks.

Purpose of the Study:

  • To formulate a mathematical framework for the phage lambda genetic switch.
  • To incorporate stochastic effects into the model.
  • To explain the stability and robustness of the genetic switch.

Main Methods:

  • Developed a mathematical framework integrating dynamical structure theory and gene regulation models.
  • Included stochastic effects, dissipation, driving force (potential), and transverse force.

Related Experiment Videos

  • Fixed molecular parameters using experimental data from wild-type and mutant phage lambda.

    • Main Results:

    • The model quantitatively agrees with experimental observations on protein number, lysogenization, and lysis frequencies.
    • Reproduces the observed robustness of the phage lambda genetic switch.
    • Identified exponential dependence of saddle point crossing rate on potential barrier height as key to stability and efficiency.
    • Positive feedback in cI repressor gene transcription, enhanced by CI dimer cooperative binding, is crucial for robustness.

    Conclusions:

    • The developed mathematical framework successfully represents a wide range of experimental phenomena for the phage lambda genetic switch.
    • Stochastic motion in a potential landscape explains the switch's stability and efficiency.
    • Positive feedback mechanisms are essential for the robustness of the phage lambda genetic switch.