Temperature control of the C. elegans circadian clock

线虫生物钟的温度控制

基本信息

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
项目类别：
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

项目摘要

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）节律控制着人类行为和生理学的多个方面（例如睡眠、情绪、体温），这些节律的破坏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，这些时钟可以受到日常光和/或温度周期的影响。人类和大多数研究的模型生物中包含这些光夹带时钟的机制是众所周知的，但人们对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周生物钟同步的关键夹带信号。我们的研究首次在模式生物秀丽隐杆线虫中发现了温度循环所夹带的昼夜节律基因，将该动物建立为时钟领域研究温度夹带时钟的新模型。线虫是研究温度响应的成熟系统；它具有清晰的神经回路，可以感知温度的微小变化，并表现出由温度循环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。目标 1 将开发一种实时自动成像系统，用于长期记录和量化温度循环诱导的线虫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温度信号感知和转导缺陷的基因突变体和菌株中的温度控制节律。该自动化系统还将允许从基因上筛选和分离改变温度引起的昼夜节律的基因的新突变。目标 2 将定义和表征温度引起的时钟的分子成分。这些组件预计将编码时钟基因和处理时钟温度信息的组件。我们将使用先进的全基因组重测序方法来识别这些分子成分。这种遗传模型生物体为理解生物钟提供了一个有吸引力的新途径，并且在线虫中鉴定出的新基因的同源物可能在高等生物中发挥作用，这些基因对于该生物钟的温度夹带是必需的。公共健康相关性：该提案将解决温度引起的昼夜节律的遗传和神经生物学基础。深入了解生物钟的内部运作及其对昼夜节律时间的影响对于更好地了解昼夜节律紊乱至关重要，例如自然体温周期的变化，这种情况常见于中风等神经系统疾病患者。