Mechanisms of noise-resistance in genetic oscillators

By Jose M. G. Vilar, H. Kueh, Naama Barkai, Stanislas Leibler. Proceedings of the National Academy of Sciences of the United States of America, 2002

635 citations recorded by the source corpus.

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. & 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.

Subfields: Endocrine and Autonomic Systems, Molecular Biology, Plant Science

View Paper: https://www.semanticscholar.org/paper/65bcc1e41f2dd528cd0b9f112725219eff07c636

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In Endocrine and Autonomic Systems

Boris N. Kholodenko

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In Plant Science

Citations in the corpus

Flow*: An Analyzer for Non-linear Hybrid Systems (2013, neutral): “58 10 Bio [15] 9 0.”
Universally Sloppy Parameter Sensitivities in Systems Biology Models (2007, methodology): “The models are ordered by increasing number of free parameters and are: (a) eukaryotic cell cycle [28], (b) Xenopus egg cell cycle [29], (c) eukaryotic mitosis [30], (d) generic circadian rhythm [31], (e) nicotinic acetylcholine intra-receptor dynamics [32], (f) generic kinase cascade [33], (g) Xeno”
Cell-signalling dynamics in time and space (2006, background): “Notably, relaxation oscillations and negative-feedback oscillations differ in their robustness to noise 71 and generally exhibit different shapes and control of the amplitude and period.”
Biological Physics of the Developing Embryo (2005, neutral): “, random biochemical fluctuations that inevitably occur during the course of embryogenesis and other biological processes (Barkai and Leibler, 2000; Vilar et al., 2002).”
Nonequilibrium Thermodynamics of Chemical Reaction Networks: Wisdom from Stochastic Thermodynamics (2016, background): “These features become crucial when considering problems such as signal transduction and biochemical switches [24, 109, 110], biochemical oscillations [28, 111], growth”
Metabolomics in systems biology. (2003, background): “The components of dynamic biochemical networks exhibit high biological variability owing to the inherent noise, fluctuations, transients, and oscillations that are part of plant homeostasis (7, 42, 52, 95, 104).”