Mechanistic studies of sickness sleep

病态睡眠的机制研究

基本信息

批准号：
10274876
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/10274876
关键词：
Address Adult Affect Afferent Neurons African Trypanosomiasis 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 Life Mammals Methods Motivation Movement Mus Mutagenesis 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 Viral Virus Diseases Withdrawal arm cytokine deprivation environmental stressor feeding fly gene function gene product genetic manipulation genome-wide interest mortality mutant paracrine prevent programs 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.

项目概要与其他动物一样，在线虫中，疾病与运动减少、活动减少有关。喂养，增加睡眠。蠕虫的疾病行为是由环境压力引起的，包括热休克、紫外线和感染。生病期间的这种行为程序是由蠕虫调节的中枢神经元被细胞因子表皮生长因子（EGF）激活。 EGF 导致活性降低在蠕虫、苍蝇、鱼和小鼠中，EGF 激活本身的机制尚不清楚。我们将利用秀丽隐杆线虫来研究疾病期间EGF的调节机制。在目标 1 中，我们将确定 EGF 在何处（从哪些细胞）以及何时释放以促进疾病行为。确定其他监管机构 EGF 激活的过程，在目标 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。在目标 3 中，我们将检验疾病行为支持疾病期间生存的假设。沿着- 这些研究的长期目标是确定用于开发诊断和治疗的候选信号分子治疗生病期间的嗜睡并了解睡眠对促进康复的重要性来自疾病。