The properties and evolvability of the cyanobacterial circadian genetic network

描述(申请人提供)：我将探索蓝藻聚球藻PCC7942昼夜节律背后的遗传网络的特性和进化，以更好地了解昼夜节律调节的分子机制、其可塑性(进化性)和基因网络的一般特性。为了做到这一点，我提出了三组实验。(1)系统地和特异地改变长链霉菌昼夜节律遗传网络中的参数(即时钟基因的丰度、稳定性和生化特性)，并量化昼夜节律的差异。这将提供一种自下而上的方法来确定这些参数对表型的相对贡献、网络对这些参数中的扰动的稳健性以及通过相对简单的改变可以推动系统具有的表型范围。(2)确定数千个单基因和双基因敲除的昼夜节律周期，以确定影响昼夜节律周期的基因的数量和程度。(3)通过在不同的明暗周期中进行选择，实验进化出具有昼夜节律变化的长穗沙门藻，以直接探索昼夜遗传网络的进化性。这里的见解将有助于我们理解 高等生物体的昼夜节律控制及其病理，以及我们对其他遗传网络的理解。

DESCRIPTION (provided by applicant): I will probe the properties and evolution of the genetic network that underlies circadian rhythm in the cyanobacteria Synechococcus elongatus PCC 7942 to better understand the molecular mechanism of circadian regulation, its plasticity (evolvability) and general properties of gene networks. To do this, I propose three sets of experiments. (1) Systematically and specifically vary parameters within the circadian genetic network in S. Elongatus (i.e. abundance, stability and biochemical properties of clock genes) and quantify differences in circadian rhythms. This will provide a bottom-up approach to determine the relative contribution of these parameters to phenotype, the robustness of the network to perturbations in these parameters, and the range of phenotypes that the system can be pushed to have with relatively simple changes. (2) Determine the circadian period of thousands of single and double gene knockouts to determine the number of genes that influence circadian period and to what extent. (3) Experimentally evolve S. elongatus to have altered circadian rhythms by selection in different light-dark cycles to directly probe the evolvability of the circadian genetic network. Insights here will be useful in our understanding of circadian control and its pathologies in higher organisms, as well as our understanding of other genetic networks.