Regulation and Significance of Sustained Circadian Oscillations

持续昼夜节律振荡的调节和意义

• 批准号: 8562033
• 负责人: CARL Hirschie JOHNSON
• 金额: $ 29.29万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8562033
• 关键词: Address; Anguish; Bacteria; Biochemical; Biochemical Reaction; Bioinformatics; Biological; Biological Assay; Biological Clocks; Biological Models; Biological Process; Cardiovascular Diseases; Characteristics; Circadian Rhythms; Coupled; Cyanobacterium; Disease; Environment; Escherichia coli; Eubacterium; Event; Evolution; Exhibits; Financial compensation; Frequencies; Future; Gene Expression Profile; Genetic; Genomics; Goals; Health; Hour; Human; Jet Lag Syndrome; Lead; Light; Maintenance; Malignant Neoplasms; Mental Depression; Mental Health; Metabolic; Metabolic Diseases; Metabolism; Molecular; Mutation; Noise; Organism; Pattern; Performance; Periodicity; Personal Satisfaction; Phase; Phenotype; Plants; Process; Property; Protocols documentation; Regulation; Schedule; Sleep; Staging; Structure; Synechococcus; System; Temperature; Testing; Time; alertness; circadian pacemaker; fitness; fungus; hormone metabolism; in vivo; novel; peroxiredoxin; physical conditioning; pressure; public health relevance; research study; response; therapy design; therapy development

DESCRIPTION (provided by applicant): Circadian (daily) rhythms are a crucial component of human health that regulates sleep, alertness, hormones, metabolism, and many other biological processes. The fascination of this phenomenon is to explain how a biochemical mechanism (i) can robustly sustain a long period (~24 h) oscillation whose frequency keeps time so precisely, and (ii) enhance fitness in the natural environment. These questions remain critically important unanswered issues in the circadian rhythms field. For example, the adaptiveness is not clear for the most obvious circadian characteristic-a robust self-sustained oscillation in constant conditions. If "anticipation" of future temporal events (e.g., dawn, dusk, etc.) is the goal of circadian timekeepers, why is a temperature-compensated "hourglass timer" that is initiated by dawn or dusk not sufficient? And yet evolution in every case has selected an oscillator that sustains itself in non-natural continuous as the timekeeper for regulating daily processes, and this characteristic forms the core defining factor for circadian rhythms. The overall hypothesis of this project is that circadian pacemakers that are self-sustained in constant environments do provide a fitness advantage in cyclic environments and that multioscillator structure contributes to the maintenance of high amplitude oscillations in vivo. Testing this hypothesis will take advantage of the unique capabilities of the eubacteria Synechococcus elongatus (cyanobacterium) and E. coli by a three-pronged approach-genetic, biochemical, and by tests of adaptive fitness. First, the adaptive value of sustained circadian oscillations will be quantified y competition assays and metabolic patterns that correlate with adaptiveness will be identified as a "signature" of the advantage conferred by sustained circadian oscillations. Second, the contributions of multioscillator organization will be assessed towards establishing (i) robust, sel-sustained oscillations, and (ii) adaptive competitiveness. Finally, a novel experimental selection approach will identify environmental pressures that can lead to the evolution of self-sustained circadian oscillations. The answers to these questions will help us to understand fundamental circadian organization and rhythmic regulation of metabolism; this understanding can help us to better design therapies for disorders in which circadian clocks are implicated.

描述（由申请人提供）：昼夜节律是人类健康的关键组成部分，可调节睡眠，机敏，激素，代谢和许多其他生物学过程。这种现象的迷恋是为了解释生化机制（i）如何能够坚固地维持长时间（约24小时）的振荡，其频率如此精确地保持时间，并且（ii）增强自然环境中的适合度。这些问题仍然在昼夜节律领域至关重要的未解决问题。例如，对于最明显的昼夜节律特征，适应性尚不清楚 - 在恒定条件下稳健的自我维持的振荡。如果对未来的时间事件（例如，黎明，黄昏等）的“预期”是昼夜节律的目标，那么为什么由黎明或黄昏发起的温度补偿的“沙漏计时器”不足？然而，在每种情况下，进化都选择了一个振荡器，该振荡器以非自然的连续状态作为调节日常过程的计时员，并且这种特征构成了昼夜节律的核心定义因素。总体假设 该项目是，在恒定环境中自我维持的昼夜节律动摇者确实在环境环境中提供了适应性优势，并且多兴趣示波器结构有助于维持体内高振幅振荡。 检验该假设将利用三pon依的方法，生化，并通过适应性的测试来利用Eubacteria synechococcus elongacoccus elongacoccus（Cyanobacterium）和大肠杆菌的独特能力。首先，将量化循环振荡的自适应值量y竞争测定法和与适应性相关的代谢模式将被确定为持续的昼夜节律振荡所赋予的优势的“签名”。其次，将评估多振荡者组织的贡献，以建立（i）（i）强大的，具有SEL的振荡和（ii）自适应竞争力。最后，一种新型的实验选择方法将确定可以导致自我维持的昼夜节律演变的环境压力。 这些问题的答案将有助于我们了解基本的昼夜节律组织和代谢的节奏调节；这种理解可以帮助我们更好地设计与昼夜节律有关的疾病的设计疗法。