title: Functioning and robustness of a bacterial circadian clock.
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.
authors.affiliation: Institute for Theoretical Biology, Humboldt University, Berlin, Germany.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Clodong
authors.forename: Ulf
authors.initials: U
authors.lastname: Dühring
authors.forename: Luiza
authors.initials: L
authors.lastname: Kronk
authors.forename: Annegret
authors.initials: A
authors.lastname: Wilde
authors.forename: Ilka
authors.initials: I
authors.lastname: Axmann
authors.forename: Hanspeter
authors.initials: H
authors.lastname: Herzel
authors.forename: Markus
authors.initials: M
authors.lastname: Kollmann
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism / Q000502:physiology; D002940:Circadian Rhythm; D056925:Circadian Rhythm Signaling Peptides and Proteins; D004591:Electrophoresis, Polyacrylamide Gel; D010766:Phosphorylation; D011485:Protein Binding; D046940:Synechococcus / Q000378:metabolism / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; D056925:Circadian Rhythm Signaling Peptides and Proteins; C114269:KaiA protein, cyanobacteria; C114270:KaiB protein, cyanobacteria; C114271:KaiC protein, cyanobacteria