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）：每日（昼夜节律）节奏控制人类行为和生理学的多个方面（例如睡眠，情绪，体温），这些节奏的破坏可能会导致或影响大多数神经系统疾病的严重性。昼夜节律是由我们的大脑和身体中的时钟驱动的，这些时钟可能会被日常的光周期和/或温度周期夹带。包括人类和所研究的大多数模型生物中的这些光入钟的机制是众所周知的，但是温度信号如何控制这些时钟。对哺乳动物的最新研究表明，自然体温循环是至关重要的夹带信号，可以使外围身体时钟保持同步。我们的研究首次发现了秀丽隐杆线虫模型中的温度周期所吸收的昼夜节律基因，将这种动物作为时钟场中的新模型建立，用于研究温度入口的时钟。秀丽隐杆线虫是研究温度反应的良好系统。它具有绘制良好的神经回路，可以感觉到温度的较小变化，并表现出温度周期引起的昼夜节律行为。该提案将使用实时成像与秀丽隐杆线虫中的遗传方法结合在一起，以及最近开发的转基因昼夜节记者来研究时钟温度进入的机制。 AIM 1将开发一种实时自动成像系统，用于长期记录和定量由温度周期诱导的秀丽隐杆线虫中基因表达中的昼夜节律。这个新的体内自动成像系统将有助于研究基因突变体中温度进入的节奏，并且在秀丽隐杆线虫中温度信号的感知和转导中有缺陷。自动化系统还将允许在改变温度入围的昼夜节律的基因中筛选和分离新的突变。 AIM 2将定义和表征温度进入时钟的分子成分。预计这些组件将编码将温度信息处理为时钟的时钟基因和组件。我们将使用先进的全基因组重新测序方法来识别这些分子成分。这种遗传模型生物提供了一种有吸引力的新途径，可以理解昼夜节律的时钟，并且在秀丽隐杆线虫中鉴定出的新基因的同源物可能是该时钟温度进入所必需的，在较高的生物体中可能起作用。 公共卫生相关性：该提案将解决温度入围昼夜节律的遗传和神经生物学基础。了解昼夜节律时钟的内部运作方式以及对昼夜节时间保持的影响至关重要，这对于更好地了解昼夜节律的节奏破坏，例如自然体温周期的变化，在神经系统疾病的患者中通常发现，例如中风。