Studies of behavioral quiescence in C. elegans

线虫行为静止的研究

• 批准号: 6931598
• 负责人: David Menassah Raizen
• 金额: $ 17.52万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-02 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6931598
• 关键词: Caenorhabditis elegans; RNA interference; adenosine; behavioral genetics; charge coupled device camera; circadian rhythms; developmental neurobiology; dopamine; gene mutation; helminth genetics; homeostasis; invertebrate locomotion; neurochemistry; neuropsychology; neuroregulation; postdoctoral investigator; protein structure function; serotonin; sleep; synaptogenesis; transcription factor

DESCRIPTION (provided by applicant): Impeding our understanding of behaviorally quiescent states such as sleep and their relationship to development is a lack of an animal model that has a well-understood anatomy in addition to powerful tools for genetic analysis of quiescence. Caenorhabditis elegans is a genetically tractable animal with an exquisitely well-understood neuroanatomy and has been used to model several processes of human disease relevance. A quiescent state occurs during lethargus, a developmentally controlled period during which there is extensive synaptogenesis in the nervous system. Dr. Raizen, the principal investigator, plans to investigate the processes and neurochemicals that control the timing and execution of this quiescent state. Specifically, he will test the roles of serotonin, dopamine, and adenosine in the control of quiescence and characterize the homeostatic control of this state. In Aim 2, he will test the hypothesis that the LIN-42 protein, the C. elegans orthologue to the circadian protein PERIOD, plays a role in the control of the timing of quiescence. In Aim 3, he will determine whether or not quiescence is required for synaptogenesis during development. These studies will compare and contrast behavioral quiescence in C. elegans to that seen in other animals and will answer the question: Can quiescence in C. elegans be considered a sleep like state? Regardless of the answer, the study will address fundamental problems in behavioral state control and its relationship to nervous system change. The studies will be performed in the laboratories of Dr. Allan Pack in the Center for Sleep and Neurobiology, and of Dr. Meera Sundaram, in the Department of Genetics. This training grant will support Dr. Raizen while he learns the scientific field of sleep and chronobiology and develops C. elegans as a model system for the study of behavioral quiescence and its relationship to development.

描述（由申请人提供）：除了缺乏用于静止遗传分析的强大工具之外，还缺乏具有良好解剖结构的动物模型，这阻碍了我们对睡眠等行为静止状态及其与发育的关系的理解。秀丽隐杆线虫是一种遗传上易驯化的动物，其神经解剖学结构非常易于理解，已被用来模拟与人类疾病相关的多种过程。静止状态发生在昏睡期间，这是一个发育控制的时期，在此期间神经系统中有广泛的突触发生。首席研究员 Raizen 博士计划研究控制这种静止状态的时间和执行的过程和神经化学物质。具体来说，他将测试血清素、多巴胺和腺苷在控制静止中的作用，并表征这种状态的稳态控制。在目标 2 中，他将测试以下假设：LIN-42 蛋白（线虫昼夜节律蛋白 PERIOD 的同源蛋白）在控制静止时间方面发挥着作用。在目标 3 中，他将确定发育过程中突触发生是否需要静止。这些研究将比较和对比线虫的行为静止与其他动物的行为静止，并回答以下问题：线虫的静止是否可以被视为类似睡眠的状态？无论答案如何，该研究都将解决行为状态控制及其与神经系统变化的关系的基本问题。这些研究将在睡眠和神经生物学中心的 Allan Pack 博士和遗传学系的 Meera Sundaram 博士的实验室中进行。这笔培训补助金将支持 Raizen 博士学习睡眠和时间生物学科学领域，并开发线虫作为研究行为静止及其与发育关系的模型系统。