Mechanistic studies of sickness sleep

病态睡眠的机制研究

基本信息

批准号：
10630175
负责人：
David Menassah Raizen
金额：
$ 40.63万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-15 至 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10630175
关键词：
Acceleration Address Adult Affect Afferent Neurons Animals Auxins Behavior Behavior Control Behavioral Biological Biological Models Caenorhabditis elegans Cells Cellular Stress Chemicals Chronic Clinical Treatment Data Defect Diagnostic Drowsiness Epidermal Growth Factor Epidermal Growth Factor Receptor Fishes Functional disorder Future Genes Genetic Genetic Transcription Goals Heat-Shock Response Human Impairment Infection Inflammatory Invertebrates Mammals Methods Motivation Movement Mus Mutagenesis Mutagens Mutate Mutation Nematoda Neurons Neurosecretory Systems Peptides Peripheral Positioning Attribute Receptor Signaling Recovery Regulation Signal Transduction Signaling Molecule Site Sleep Sleep Deprivation Source Stream Stress Symptoms System Testing Time Translating Ultraviolet Rays Uncertainty Vertebrates Viral Virus Diseases Withdrawal arm candidate identification cytokine deprivation environmental stressor feeding fly gene function gene product genetic manipulation genome-wide interest mortality mutant paracrine prevent programs sleep behavior social tool whole genome

项目摘要

Project Summary In the nematode C. elegans as in other animals, sickness is associated with reduced movement, reduced feeding, and increased sleep. Sickness behavior in worms is induced by environmental stressors including heat shock, ultraviolet light, and infection. This behavioral program during sickness is regulated by worm central neurons that are activated by the cytokine epidermal growth factor (EGF). EGF causes reduced activity in worms, flies, fish, and mice, but the mechanisms of EGF activation itself during sickness are not clear. We will use C. elegans to study the mechanism of EGF regulation during sickness. In Aim 1, we will determine where (from which cells) and when EGF is released to promote sickness behavior. To identify other regulators of EGF activation, in Aim 2, we will perform genome-wide discovery screens for genes required for sickness behavior. In Aim 3, we will test the hypothesis that sickness behavior supports survival during sickness. A long- term goal of these studies is to identify candidate signaling molecules for developing diagnostics and treatments of sleepiness during sickness and to understand the importance of sleep in promoting recovery from illness.

项目摘要与其他动物一样进食和增加睡眠。蠕虫的疾病行为是由环境压力引起的热休克，紫外线和感染。疾病期间的行为计划受蠕虫的调节被细胞因子表皮生长因子（EGF）激活的中枢神经元。 EGF导致活动减少在蠕虫，苍蝇，鱼类和小鼠中，但是疾病期间EGF激活本身的机制尚不清楚。我们将使用秀丽隐杆线虫研究疾病期间EGF调节的机制。在AIM 1中，我们将确定在其中（从哪个细胞）释放EGF以促进疾病行为。确定其他监管机构在EGF激活中，在AIM 2中，我们将对疾病所需的基因进行全基因组发现筛选行为。在AIM 3中，我们将检验以下假设：疾病行为支持疾病期间的生存。沿着- 这些研究的术语目标是确定用于开发诊断和的候选信号分子疾病期间嗜睡的疗法，并了解睡眠在促进康复方面的重要性从疾病中。