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.

项目总结/文摘