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Functioning and robustness of a bacterial circadian clock
by:In: MOLECULAR SYSTEMS BIOLOGY, Vol. 3
(2007)
.
Abstract
Cyanobacteria are the simplest known cellular systems that regulate
their biological activities in daily cycles. For the cyanobacterium
Synechococcus elongatus, it has been shown by in vitro and in vivo
experiments that the basic circadian timing process is based on
rhythmic phosphorylation of KaiC hexamers. Despite the excellent
experimental work, a full systems level understanding of the in vitro
clock is still lacking. In this work, we provide a mathematical
approach to scan different hypothetical mechanisms for the primary
circadian oscillator, starting from experimentally established
molecular properties of the clock proteins. Although optimised for
highest performance, only one of the in silico-generated reaction
networks was able to reproduce the experimentally found high amplitude
and robustness against perturbations. In this reaction network, a
negative feedback synchronises the phosphorylation level of the
individual hexamers and has indeed been realised in S. elongatus by
KaiA sequestration as confirmed by experiments.


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