Regulation and Significance of Sustained Circadian Oscillations

项目摘要/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、荷尔蒙、新陈代谢和许多其他生物过程。这件事的魅力 这一现象是用来解释生化机制(I)如何能够长期持续的。 (~24小时)振荡，其频率如此精确地保持时间，以及(Ii)增强了在 自然环境。这些问题仍然是世界上极其重要的悬而未决的问题 昼夜节律场。例如，对于最明显的情况，自适应值并不清楚 昼夜节律特征--在恒定条件下的强健的自我维持的振荡。如果“预期” 未来时间事件(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式“沙漏计时器”还不够吗？和 然而，进化无处不在地选择了一种振荡器，这种振荡器在非自然的连续状态下维持自己 用于调整日常流程的计时器，这一特征形成了定义的核心 昼夜节律的特性。该项目的总体目标是确定 节律环境的特征提供了选择性压力，使细胞 组织基因表达和代谢以促进昼夜节律特性 守时。识别可能导致生物进化的选择压力和进化步骤 守时将使我们能够更深刻地理解昼夜节律机制和 方式(S)他们可能会得到加强，以帮助人类的健康和表现。 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，在自由生命有机体中，健康测试，转录组分， 生物化学将决定新陈代谢条件是否决定持续振荡器是否 必然是适应性的。第二，宿主/微生物群关系的时间维度将是 被操纵以确定肠道微生物群是否处于主动选择的计时能力之下。 最后，一种新的实验选择方法将确定哪些环境压力 能够进化出生物钟。 这些问题的答案将有助于我们更好地理解 新陈代谢的基本昼夜节律组织和节律调节；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。

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.