Environmental and molecular noise buffering by the cyanobacterial clock in individual cells

Aleksandra Eremina, Christian Schwall, Teresa Saez, Lennart Witting, Dietrich Kohlheyer, Bruno M. C. Martins (), Philipp Thomas () and James C. W. Locke ()
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Aleksandra Eremina: University of Cambridge
Christian Schwall: University of Cambridge
Teresa Saez: University of Cambridge
Lennart Witting: Forschungszentrum Jülich
Dietrich Kohlheyer: Forschungszentrum Jülich
Bruno M. C. Martins: University of Warwick
Philipp Thomas: Imperial College London
James C. W. Locke: University of Cambridge

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: Abstract Circadian clocks enable organisms to anticipate daily cycles, while being robust to molecular and environmental noise. Here, we show how the clock of the cyanobacterium Synechococcus elongatus PCC 7942 buffers genetic and environmental perturbations through its core KaiABC phosphorylation loop. We first characterise single-cell clock dynamics in clock mutants using a microfluidics device that allows precise control of the microenvironment. We find that known clock regulators are dispensable for clock robustness, whilst perturbations of the core clock reveal that the wild type operates at a noise optimum that we can reproduce in a stochastic model of just the core phosphorylation loop. We then examine how the clock responds to noisy environments, including natural light conditions. The model accurately predicts how the clock filters out environmental noise, including fast light fluctuations, to keep time while remaining responsive to environmental shifts. Our findings illustrate how a simple clock network can exhibit complex noise filtering properties, advancing our understanding of how biological circuits can perform accurately in natural environments.

Date: 2025
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DOI: 10.1038/s41467-025-58169-8

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