Project 3

线虫生物钟的温度控制 日常(昼夜)节律控制着人类行为和生理的多个方面(例如，睡眠、身体 体温)和这些节律的中断会导致或影响大多数神经系统的严重程度 中风和阿尔茨海默氏症等疾病。这些昼夜节律是由我们大脑中的时钟驱动的 以及可能被日常光线和/或温度循环缠绕的身体。深入的分析已经确定 在人类和大多数模式生物中，组成这些光携带时钟的生理机制 研究过，但温度信息如何控制这些时钟尚不清楚。我们的研究已经确立了 线虫线虫作为一种强大的遗传模型系统研究线虫的温度控制 钟。在这项拟议的研究中，我们将使用遗传和基因组方法以及实时成像 在线虫中研究温度控制的分子机制和神经通路 生物钟的一部分。特定目标1将开发一种新的实时成像系统，用于记录和 对自由活动的线虫行为和基因表达的昼夜节律性进行量化。这一成像 为时钟突变体的突变分析和遗传筛选奠定了基础。具体目标2将定义 将温度信息传输到时钟的感觉神经元类型(S)。这将有助于理解 将环境信息处理并整合到时钟中的感觉通路。具体目标3将 定义时钟的分子组成。这些组件预计将针对核心时钟进行编码 处理从核心时钟到时钟输出基因的温度信息的基因和组件。 特定目标4将通过mRNA测序来识别在单一感觉神经元类型中表达的昼夜节律基因。 线虫时钟Will调控的全套感觉基因的鉴定 确定处理环境的基因差异表达的行为后果 将信息发送到时钟。深入了解生物钟的内部工作原理和 对昼夜节律的影响应该为我们提供新的治疗或预防 昼夜节律紊乱的神经行为后果。

Temperature control of the C. elegans circadian clock Daily (circadian) rhythms control multiple aspects of human behavior and physiology (e.g. sleep, body temperature) and disruption of these rhythms can either cause or affect the severity of most neurological disorders such as stroke and Alzheimer's disease. These circadian rhythms are driven by clocks in our brain and body that can be entrained by daily light and/or temperature cycles. In depth analyses have identified the physiological mechanisms comprising these light-entrained clocks in humans and most model organisms studied, but how temperature information controls these clocks is unclear. Our research has established the nematode Caenorhabditis elegans as a powerful genetic model system to study temperature control of the clock. In this proposed research, we will use genetic and genomic approaches as well as real-time imaging in C elegans to investigate the molecular mechanisms and neural pathways underlying temperature control ofthe circadian clock. Specific Aim 1 will develop a new real-time imaging system for recording and quantifying circadian rhythmicity in behavior and gene expression in freely moving C elegans. This imaging will be useful for mutant analysis and genetic screening of clock mutants. Specific Aim 2 will define the sensory neuron types that transmit temperature information to the clock(s). This will aid in understanding the sensory pathways that process and integrate environmental information to the clock. Specific Aim 3 will define the molecular components ofthe clock. These components are expected to encode for core-clock genes and components that process temperature information from the core-clock to clock-output genes. Specific Aim 4 will identify circadian genes expressed in single sensory neuron types with mRNAsequencing. Identification ofthe complete set of sensory genes regulated by the C elegans clock will determine the behavioral consequences of differential expression of genes that process environmental information to the clock. Understanding the inner workings ofthe circadian clock in great depth and the impacts on circadian time keeping should provide us with new avenues of treatment or prevention of neurobehavioral consequences of disrupted circadian timing.