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Related Experiment Videos

Positive-feedback loops as a flexible biological module.

Nicholas T Ingolia1, Andrew W Murray

  • 1Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.

Current Biology : CB
|April 3, 2007
PubMed
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We engineered a bistable genetic switch in yeast using positive feedback. This system demonstrates memory and decision-making, with mutations altering its behavior and matching model predictions.

Area of Science:

  • Molecular Biology
  • Systems Biology
  • Genetics

Background:

  • Bistability in genetic networks enables cellular memory and discrete responses to continuous signals.
  • Positive feedback is a key mechanism for achieving bistability, but feedback loops have diverse roles in signal transduction.

Purpose of the Study:

  • To engineer a bistable genetic system in budding yeast by introducing positive feedback into the pheromone response pathway.
  • To investigate how quantitative changes in feedback promoter expression affect system behavior.
  • To model the positive-feedback system and compare simulation results with experimental data.

Main Methods:

  • Introduction of a positive feedback loop into the budding yeast pheromone response pathway.
  • Generation of mutations to modulate basal and induced expression levels of the feedback promoter.

Related Experiment Videos

  • Development and application of a simple stochastic model for system simulation.

    • Main Results:

    • The engineered system exhibited bistability, showing persistent pathway activation at high pheromone levels and heterogeneous responses at lower levels.
    • Mutations quantitatively altered expression levels, leading to qualitative changes in system behavior.
    • Simulations of the stochastic model closely matched experimental observations.

    Conclusions:

    • Positive feedback loops can generate diverse behaviors, including bistability, within genetic networks.
    • Simple mutations can induce switches between different system behaviors.
    • The engineered system provides a model for understanding cellular memory and decision-making.