Mechanisms of noise-resistance in genetic oscillators

Model Status

This CellML modelis known to run in OpenCell and COR to reproduce the results published in the paper on which it is based (figures 2 and 3).

Model Structure

ABSTRACT: A wide range of organisms use circadian clocks to keep internal sense of daily time and regulate their behavior accordingly. Most of these clocks use intracellular genetic networks based on positive and negative regulatory elements. The integration of these "circuits" at the cellular level imposes strong constraints on their functioning and design. Here, we study a recently proposed model [Barkai, N. and Leibler, S. (2000) Nature (London), 403, 267-268] that incorporates just the essential elements found experimentally. We show that this type of oscillator is driven mainly by two elements: the concentration of a repressor protein and the dynamics of an activator protein forming an inactive complex with the repressor. Thus, the clock does not need to rely on mRNA dynamics to oscillate, which makes it especially resistant to fluctuations. Oscillations can be present even when the time average of the number of mRNA molecules goes below one. Under some conditions, this oscillator is not only resistant to but, paradoxically, also enhanced by the intrinsic biochemical noise.

The original paper reference is cited below:

Mechanisms of noise-resistance in genetic oscillators, Jose M. G. Vilar, Hao Yuan Kueh, Naama Barkai, and Stanislas Leibler, 2002,Proceedings of the National Academy of Sciences of the United States of America, 99, 5988-5992. PubMed ID: 11972055

Biochemical network of the circadian oscillator model.