The properties and evolvability of the cyanobacterial circadian genetic network

蓝藻昼夜节律遗传网络的特性和进化性

• 批准号: 8254581
• 负责人: Ryan K Shultzaberger
• 金额: $ 5.22万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8254581
• 关键词: Affect; Bacteria; Biochemical; Biological Assay; Biological Process; Circadian Rhythms; Cloning; Computers; Core Protein; Cyanobacterium; DNA Sequence; Gene Expression; Gene Expression Regulation; Genes; Genetic; Hour; Human; In Vitro; Individual; Knock-out; Libraries; Light; Luciferases; Measures; Molecular; Organism; Other Genetics; Output; Pathology; Pharmaceutical Preparations; Phenotype; Phosphorylation; Property; Proteins; Randomized; Regulation; Relative (related person); Resistance; Source; Synechococcus; System; Variant; charge coupled device camera; fitness; gene interaction; genetic evolution; insight; knockout gene; luminescence; mutant; pressure; promoter; reconstitution; research study

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. PUBLIC HEALTH RELEVANCE: Circadian control over biological processes is present in a wide range of species (from humans to bacteria), and disruptions to the underlying molecular clock or the genetic network that it is contained within can adversely affect organismal fitness. This project aims to systematically perturb the circadian genetic network in the cyanobacteria Synechococcus elongatus PCC 7942 and quantify the effects of these changes on circadian period to better understand the molecular mechanism of circadian regulation and general properties of genetic networks. Insights here will be useful in our understanding of circadian control and its pathologies in higher organisms.

描述（由申请人提供）：我将探测蓝细菌细长聚球藻PCC 7942中的昼夜节律的遗传网络的性质和进化，以更好地理解昼夜节律调节的分子机制、其可塑性（进化性）和基因网络的一般性质。为此，我提出了三组实验。(1)系统地和具体地改变参数的昼夜遗传网络在S。Elongatus（即生物钟基因的丰度、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，网络对这些参数扰动的鲁棒性，以及系统可以通过相对简单的变化被推到的表型范围。(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)实验性地进化S. elongatus通过选择不同的光暗周期来改变昼夜节律，以直接探测昼夜遗传网络的进化能力。这里的见解将有助于我们理解 昼夜节律控制及其在高等生物中的病理学，以及我们对其他遗传网络的理解。 公共卫生关系：生物过程的昼夜节律控制存在于广泛的物种（从人类到细菌）中，对潜在的分子钟或其所包含的遗传网络的破坏会对生物体的适应性产生不利影响。本项目旨在系统地扰动蓝细菌Synechococcus elongatus PCC 7942的昼夜节律遗传网络，并量化这些变化对昼夜节律周期的影响，以更好地理解昼夜节律调节的分子机制和遗传网络的一般特性。这里的见解将有助于我们理解高等生物的昼夜节律控制及其病理学。