Regulation and Significance of Sustained Circadian Oscillations

持续昼夜节律振荡的调节和意义

• 批准号: 9976535
• 负责人: CARL Hirschie JOHNSON
• 金额: $ 30.61万
• 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 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9976535
• 关键词: Address; Aerobic; Alpha Rhythm; Bacteria; Bacterial Model; Biochemical; Biochemical Reaction; Biochemistry; Bioinformatics; Biological; Biological Clocks; Biological Models; Biological Process; Cardiovascular Diseases; Characteristics; Circadian Rhythms; Clock protein; Complex; Coupled; Dimensions; Disease; Environment; Environmental Risk Factor; Escherichia coli; Event; Evolution; Feeding Patterns; Financial compensation; Frequencies; Future; Gene Expression; Gene Expression Regulation; Gene Structure; Genes; Genetic; Genomics; Goals; Health; Hour; Human; Jet Lag Syndrome; Lead; Malignant Neoplasms; Mental Depression; Mental Health; Mental disorders; Metabolic; Metabolic Diseases; Metabolism; Molds; Molecular; Mutation; Natural Selections; Organism; Pattern; Performance; Periodicity; Personal Satisfaction; Phase; Process; Property; Proteins; Protocols documentation; Public Health; Regulation; Role; Schedule; Sleep; System; Temperature; Testing; Time; Variant; alertness; circadian; circadian pacemaker; fascinate; fitness; fitness test; gut microbiome; hormone metabolism; host microbiome; improved; microbial community; microbiome composition; novel; physical conditioning; pressure; progenitor; response; shift work; therapy design; therapy development; transcriptome; transcriptomics

Project Summary/Abstract: 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 adaptive value 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 ubiquitously selected an oscillator that sustains itself in non-natural continuous as the timekeeper for regulating daily processes, and this characteristic forms a core defining property of circadian rhythms. The overall goal of this project is to determine which characteristics of rhythmic environments provide selective pressures that direct cellular organization of gene expression and metabolism to promote properties of circadian timekeeping. Identifying the selective pressures & evolutionary steps that can lead to biological timekeeping will enable a more profound understanding of circadian mechanisms and the way(s) they might be reinforced to aid human health and performance. The unique characteristics of model systems will be harnessed to attain the goal of this project by a multifaceted approach. First, in free-living organisms, fitness tests, transcriptomics, and biochemistry will determine if metabolic conditions dictate whether sustained oscillators are necessarily adaptive. Second, the temporal dimensions of host/microbiome relations will be manipulated to ascertain if the gut microbiome is under active selection for timekeeping ability. Finally, a novel experimental selection approach will identify which environmental pressures are capable of evolving circadian clocks. The answers to these questions will help us to better understand general principles of 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.

项目概要/摘要： 昼夜节律是调节睡眠的人类健康的重要组成部分， 警觉性、激素、新陈代谢和许多其他生物过程。这个的魅力在于 现象是解释生物化学机制（i）如何能够有力地维持长时间 （~24小时）振荡，其频率保持时间如此精确，和（ii）提高健身在 自然环境这些问题仍然是至关重要的悬而未决的问题， 昼夜节律场例如，最明显的自适应值并不明确 昼夜节律特征-在恒定条件下的稳健的自我维持振荡。如果“预期” 未来的时间事件（例如，黎明、黄昏等）是昼夜节律计时员的目标，为什么 由黎明或黄昏启动的温度补偿“沙漏计时器”还不够吗？和 然而，进化无处不在地选择了一个振荡器，以非自然的连续方式维持自己， 用于调节日常流程的计时器，这一特征形成了一个核心定义 昼夜节律的特性。本项目的总体目标是确定 节奏环境的特征提供了选择性压力， 基因表达和代谢的组织以促进昼夜节律的特性 烦透了.识别选择压力和进化步骤，可以导致生物学 计时将使人们能够更深刻地理解昼夜节律机制和 它们可能被加强以帮助人类健康和表现的方式。 将利用模型系统的独特特性来实现这一目标。 通过多方面的方法进行项目。首先，在自由生活的生物体中，适应性测试，转录组学， 生物化学将决定代谢条件是否决定持续振荡器是否 必然是适应性的。其次，宿主/微生物组关系的时间维度将是 操作以确定肠道微生物组是否处于计时能力的主动选择下。 最后，一种新的实验选择方法将确定哪些环境压力是 能够进化生物钟。 这些问题的答案将有助于我们更好地理解 基本的昼夜节律组织和新陈代谢的节奏调节;这种理解 可以帮助我们更好地设计治疗与生物钟有关的疾病的方法。