Clodong Sébastien, Dühring Ulf, Kronk Luiza, Wilde Annegret, Axmann Ilka, Herzel Hanspeter, Kollmann Markus
Institute for Theoretical Biology, Humboldt University, Berlin, Germany.
Mol Syst Biol. 2007;3:90. doi: 10.1038/msb4100128. Epub 2007 Mar 13.
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.
蓝藻是已知的最简单的细胞系统，它们以每日周期调节自身的生物活动。对于细长聚球藻这种蓝藻，体外和体内实验表明，基本的昼夜节律计时过程基于KaiC六聚体的节律性磷酸化。尽管有出色的实验工作，但仍缺乏对体外生物钟的完整系统层面的理解。在这项工作中，我们提供了一种数学方法，从生物钟蛋白已通过实验确定的分子特性出发，扫描初级昼夜节律振荡器的不同假设机制。尽管为实现最高性能进行了优化，但计算机生成的反应网络中只有一个能够重现实验发现的高振幅以及对干扰的稳健性。在这个反应网络中，负反馈使各个六聚体的磷酸化水平同步，并且实验已证实，细长聚球藻中确实通过KaiA隔离实现了这种负反馈。
