Temperature control of the C. elegans circadian clock

线虫生物钟的温度控制

• 批准号: 8445997
• 负责人: Alexander Martinus Van der Linden
• 金额: $ 19.1万
• 依托单位: UNIVERSITY OF NEVADA RENO
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8445997
• 关键词: Address; Affect; Afferent Neurons; Animal Model; Animals; Behavior; Biological Assay; Biological Clocks; Biological Models; Body Temperature; Body Temperature Changes; Brain; Brain region; Caenorhabditis elegans; Candidate Disease Gene; Cells; Central Nervous System Diseases; Circadian Rhythms; Code; Complex; Cues; Disease; Esthesia; Etiology; Exhibits; Fluorescence; Gene Components; Gene Expression; Gene Expression Profiling; Genes; Genetic; Genetic Models; Genetic Screening; Genome; Heat-Shock Response; Homologous Gene; Hormonal; Hour; Human; Image; Light; Mammals; Maps; Measurement; Measures; Mediating; Modeling; Molecular; Monitor; Moods; Mutation; Neural Pathways; Neurobiology; Neurons; Organism; Output; Pathway interactions; Patients; Perception; Peripheral; Physiological; Physiology; Play; Process; Property; Reader; Reporter; Reporter Genes; Research; Role; Screening procedure; Secondary to; Severities; Signal Pathway; Signal Transduction; Sleep; Stroke; System; Temperature; Testing; Time; Tissues; Transgenic Organisms; Work; base; circadian pacemaker; field study; fly; in vivo; insight; mutant; nervous system disorder; neural circuit; novel; response; suprachiasmatic nucleus

DESCRIPTION (provided by applicant): Daily (circadian) rhythms control multiple aspects of human behavior and physiology (e.g. sleep, mood, body temperature), and disruption of these rhythms can either cause or affect the severity of most neurological disorders. Circadian rhythms are driven by clocks in our brain and body that can be entrained by daily light and/or temperature cycles. Mechanisms comprising these light-entrained clocks in humans and most model organisms studied are well known, but how temperature signals control these clocks is poorly understood. Recent studies in mammals have demonstrated that natural body temperature cycles are crucial entrainment signals for keeping peripheral body clocks in sync. Our research has discovered for the first time circadian genes entrained by temperature cycles in the model organism Caenorhabditis elegans, establishing this animal as a new model in the clock field for studying the temperature-entrained clock(s). C. elegans is a well- established system to study temperature responses; it has a well-mapped neural circuitry that senses small changes in temperature, and exhibits circadian behavior induced by temperature cycles. This proposal will use real-time imaging combined with genetic approaches in C. elegans and a recently developed transgenic circadian reporter to investigate the mechanisms underlying temperature-entrainment of the clock(s). Aim 1 will develop a real-time automated imaging system for long-term recording and quantification of circadian rhythms in gene expression in C. elegans induced by temperature cycles. This new in vivo automated imaging system will be useful for studying temperature-entrained rhythms in genetic mutants and strains defective in perception and transduction of temperature signals in C. elegans. The automated system will also allow to genetically screen and isolate new mutations in genes that change temperature-entrained circadian rhythms. Aim 2 will define and characterize the molecular components of the temperature-entrained clock(s). These components are expected to be coding for clock genes and components that process temperature information to the clock(s). We will use advanced whole-genome re-sequencing approaches to identify these molecular components. This genetic model organism provides an attractive new avenue for understanding the circadian clock, and it is possible that homologs of new genes identified in C. elegans that are necessary for temperature-entrainment of this clock may function in higher organisms. PUBLIC HEALTH RELEVANCE: This proposal will address the genetic and neurobiological basis of temperature-entrained circadian rhythms. Understanding the inner workings of the circadian clock in great depth and the impacts on circadian time keeping is crucial in better understanding circadian rhythm disruptions, such as changes in natural body temperature cycles, commonly found in patients with neurological disorders, such as stroke.

描述（由申请人提供）：日常（昼夜节律）节律控制着人类行为和生理的多个方面（例如睡眠、情绪、体温），这些节律的中断可能导致或影响大多数神经系统疾病的严重程度。昼夜节律是由我们大脑和身体中的时钟驱动的，这些时钟可以被每天的光线和/或温度循环所左右。在人类和大多数被研究的模式生物中，构成这些光携带时钟的机制是众所周知的，但温度信号如何控制这些时钟却知之甚少。最近对哺乳动物的研究表明，自然体温周期是保持外围生物钟同步的关键信号。本研究首次在模式生物秀丽隐杆线虫（Caenorhabditis elegans）中发现了温度循环携带的昼夜节律基因，为该动物在生物钟领域的研究奠定了新的模式。秀丽隐杆线虫是研究温度响应的成熟系统；它有一个映射良好的神经回路，可以感知温度的微小变化，并表现出由温度周期引起的昼夜节律行为。该提案将使用实时成像结合线虫的遗传方法和最近开发的转基因昼夜节律报告器来研究时钟温度夹带的机制。Aim 1将开发一种实时自动成像系统，用于长期记录和定量秀丽隐杆线虫在温度循环诱导下基因表达的昼夜节律。这种新的体内自动成像系统将有助于研究秀丽隐杆线虫中温度信号感知和转导缺陷的基因突变体和菌株的温度携带节律。自动化系统还将允许从基因上筛选和分离改变温度影响的昼夜节律的基因中的新突变。目标2将定义和表征带温时钟的分子成分。这些组件被认为是时钟基因和处理温度信息到时钟的组件的编码。我们将使用先进的全基因组重测序方法来鉴定这些分子成分。这种遗传模式生物为理解昼夜节律钟提供了一个有吸引力的新途径，并且在秀丽隐杆线虫中发现的新基因的同源物很可能在高等生物中起作用，这些基因是昼夜节律钟温度携带所必需的。