Experimental Evolution of Circadian Oscillators

昼夜节律振荡器的实验进化

• 批准号: 7901674
• 负责人: CARL Hirschie JOHNSON
• 金额: $ 30.71万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7901674
• 关键词: Back; Biological Clocks; Biological Pacemakers; Biological Rhythm; Cardiovascular Diseases; Cell Cycle; Cell division; Cells; Characteristics; Chronobiology; Circadian Rhythms; Coupled; Disease; Event; Evolution; Financial compensation; Gene Expression; Genetic; Health; Human; Lead; Link; Mental Depression; Metabolic; Metabolic Pathway; Metabolic syndrome; Metabolism; Obesity; Organism; Personal Satisfaction; Phase; Process; Public Health; Recording of previous events; Recruitment Activity; Regulation; Reporter; Shapes; Sleep; Systems Biology; Temperature; Time; cdc Genes; circadian pacemaker; feeding; luminescence; pressure; programs; public health relevance

DESCRIPTION (provided by applicant): Circadian (daily) rhythms are a crucial component of human health. Inappropriate daily regulation/phasing of sleep and other clock-controlled parameters is associated with several types of depression, obesity/metabolic syndrome, and cardiovascular disease. At the cellular level, circadian pacemakers regulate cell division, metabolism, and gene expression networks. The selective pressures that led to the evolution of the special characteristics of circadian rhythms (esp. their precise 24 h time constant and temperature compensation) have not been identified. How can metabolic processes that intrinsically feed back with short time constants be recruited by selective pressures to the establishment of a self-sustained 24 h oscillator that is temperature compensated? The answer to this question has broad significance to our understanding of cell cycles, gene transcriptional networks, "Systems" biology, evolutionary processes, and chronobiology. This project will undertake an experimental evolution of biological rhythms that have circadian characteristics in a quest to identify relevant selective pressures and whether particular metabolic pathways are predisposed towards the evolution of self-sustained biological oscillators. Single cell organisms with genetic capabilities will be subjected to a variety of environmental cycles (light/dark, UV- B, temperature) to ascertain which conditions can lead to the evolution of biological oscillators with circadian characteristics. The successful evolution of such oscillators will be assessed with luminescence reporters of cell cycle and metabolic events. PUBLIC HEALTH RELEVANCE: Circadian rhythms organize the temporal activities of metabolism and gene expression; disruption of these daily programs has serious consequences for human health and well-being. Identifying the selective pressures that can shape metabolism to establish biological clocks will enable the understanding of the history whereby clock mechanisms were developed and how clocks are coupled to metabolism. Ultimately, knowing these links may help to provide therapies for diseases that are related to clock disruption.

描述（由申请人提供）：昼夜节律是人类健康的关键组成部分。睡眠和其他时钟控制参数的每日调节/平差与几种类型的抑郁，肥胖/代谢综合征和心血管疾病有关。在细胞水平上，昼夜节律制造商调节细胞分裂，代谢和基因表达网络。尚未确定导致导致昼夜节律特殊特征演变的选择性压力（尤其是其精确的24小时时间常数和温度补偿）。如何通过选择性压力来建立自我维持的24 h振荡器（温度得到补偿）的选择性压力来募集以短时常数为代谢的代谢过程？这个问题的答案对我们对细胞周期，基因转录网络，“系统”生物学，进化过程和计时生物学的理解具有广泛的意义。该项目将对具有昼夜节律特征的生物节奏进行实验进化，以寻求确定相关的选择性压力，以及特定的代谢途径是否倾向于自我维持的生物振荡器的进化。具有遗传能力的单细胞生物将受到多种环境周期（轻/黑，紫外，温度），以确定哪些条件可能导致具有昼夜节律特征的生物振荡器的演变。这种振荡器的成功演变将通过细胞周期和代谢事件的发光记者进行评估。公共卫生相关性：昼夜节律组织新陈代谢和基因表达的时间活动；这些日常计划的破坏对人类健康和福祉产生了严重的影响。确定可以塑造新陈代谢以建立生物钟的选择性压力将使人们能够理解时钟机制的历史以及如何与新陈代谢耦合。最终，了解这些链接可能有助于为与时钟中断有关的疾病提供疗法。