Regulation and Significance of Sustained Circadian Oscillations

持续昼夜节律振荡的调节和意义

• 批准号: 10625380
• 负责人: CARL Hirschie JOHNSON
• 金额: $ 32.48万
• 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 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10625380
• 关键词: Address; Antibiotics; Bacteria; Bacterial Model; Biochemical; Biochemical Reaction; Bioinformatics; Biological; Biological Clocks; Biological Models; Biological Process; Cardiovascular Diseases; Cell Line; Cell physiology; Cells; Characteristics; Circadian Rhythms; Compensation; Complex; Cyanobacterium; Dimensions; Disease; Environment; Environmental Risk Factor; Escherichia coli; Event; Evolution; Feeding Patterns; Frequencies; Future; Gene Expression; Gene Structure; Genes; Genetic; Genomics; Goals; Growth; Health; Homeostasis; Hormones; Hour; Human; Jet Lag Syndrome; Knowledge; Malignant Neoplasms; Mental Depression; Mental Health; Mental disorders; Metabolic Diseases; Metabolism; Metagenomics; Molds; Molecular; Mutation; Natural Selections; Network-based; Organism; Performance; Periodicity; Personal Satisfaction; Phase; Photoperiod; Process; Proliferating; Property; Protocols documentation; Public Health; Recovery; Regulation; Role; Seasons; Signal Transduction; Sleep; System; Temperature; Testing; Time; alertness; cell community; cell growth regulation; circadian; circadian pacemaker; circadian regulation; cold stress; feeding; fitness; fitness test; gut microbiome; host-microbe interactions; improved; information processing; microbiome; novel; photoperiodicity; physical conditioning; pressure; progenitor; response; shift work; temporal measurement; therapy design; therapy development; transcriptome; transcriptomics

Project Summary/Abstract Circadian (daily) rhythms are a crucial component of human health that regulates sleep, alertness, homeostasis, cellular signaling, 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 conditions 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 coordinate cellular organization of gene expression and information processing 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 signaling so that 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, the circadian regulation of seasonal responses and circadian interactions within communities of cells will be investigated to determine why 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 evolution approach will identify which environmental pressures can be selective for circadian clocks. The answers to these questions will help us to better understand general principles of fundamental circadian organization and rhythmic regulation of cellular physiology; this understanding can help us to better design therapies for disorders in which circadian clocks are implicated.

项目摘要/摘要 昼夜节律是人类健康的关键组成部分，可调节睡眠，机敏， 稳态，细胞信号传导和许多其他生物过程。这种现象的迷恋是 解释生化机制（i）如何坚持长时间（约24小时）的振荡 频率使时间保持如此精确，并且（ii）增强自然环境中的适应性。这些问题仍然存在 在昼夜节律领域中至关重要的未解决问题。例如，自适应值不是 对于最明显的昼夜节律特征清楚 - 在恒定条件下稳健的自我维持的振荡。如果 对未来临时事件的“期待”（例如，黎明，黄昏等）是昼夜节律的目标，为什么 由黎明或黄昏发起的温度补偿的“沙漏计时器”不够？但进化 普遍选择在非天然连续条件下自杀的振荡器 调节日常过程，并且这种特征构成了昼夜节律定义特性的核心。 该项目的总体目标是确定节奏环境的哪些特征可提供选择性 协调基因表达和信息处理的细胞组织以促进的压力 昼夜节律的特性。确定可以导致的选择性压力和进化步骤 生物计时工作将使对昼夜节律机制和信号的更深刻理解 他们可能会得到加强以帮助人类的健康和绩效。 将利用模型系统的独特特征来实现该项目的目标 多方面的方法。首先，在自由生活的生物中，昼夜节律对季节性反应和 将研究细胞社区内的昼夜节律相互作用，以确定为什么持续的振荡器是 一定是适应性的。其次，将操纵宿主/微生物组关系的临时维度 确定肠道微生物组是否处于主动选择方面，以获得计时能力。最后，一个新颖的实验 进化方法将确定哪些环境压力可以选择昼夜节律。 这些问题的答案将有助于我们更好地理解基本的一般原则 昼夜节律组织和节奏的细胞生理调节；这种理解可以帮助我们改善 涉及昼夜节律时钟的疾病设计疗法。