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Related Experiment Videos

Modeling circadian oscillations with interlocking positive and negative feedback loops.

P Smolen1, D A Baxter, J H Byrne

  • 1Department of Neurobiology and Anatomy, W. M. Keck Center for the Neurobiology of Learning and Memory, The University of Texas-Houston Medical School, Houston, Texas 77225, USA.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|August 23, 2001
PubMed
Summary

Circadian rhythms in Neurospora and Drosophila are generated by transcriptional feedback loops. Models show that negative feedback is essential, while positive feedback is not required for robust circadian oscillations.

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Area of Science:

  • Chronobiology
  • Systems Biology
  • Molecular Biology

Background:

  • Transcriptional regulation involving positive and negative feedback loops is crucial for circadian rhythms.
  • Mathematical modeling provides a framework for understanding the complex mechanisms underlying biological oscillators.

Purpose of the Study:

  • To test the sufficiency of proposed positive and negative feedback mechanisms in generating circadian rhythms.
  • To model the circadian oscillators of Neurospora crassa and Drosophila melanogaster using differential equations.

Main Methods:

  • Construction of two differential equation-based models for Neurospora and Drosophila circadian systems.
  • Incorporation of known regulatory interactions, including transcriptional activation and repression.
  • Inclusion of time delays to represent unmodeled processes like transcription and translation.

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Main Results:

  • Both models successfully generated robust circadian oscillations, resilient to parameter changes and noise.
  • The models demonstrated entrainment to simulated light/dark cycles.
  • Circadian oscillations were maintained even after the removal of positive feedback loops in both models.

Conclusions:

  • Negative feedback loops are sufficient for generating robust circadian oscillations.
  • Positive feedback loops, while present, are not essential for the core oscillatory mechanism.
  • Time delays are critical for the generation of circadian rhythms in these models.