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Genetic Analysis of Sleep Regulation

睡眠调节的基因分析

基本信息

批准号：
9900876
负责人：
Mark N Wu
金额：
$ 35.82万
依托单位：
JOHNS HOPKINS UNIVERSITY
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 2021-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9900876
关键词：
Address Adverse effects Affect Area Arousal Astrocytes Behavior Behavioral Biological Biological Assay Cell membrane Cells Circadian Dysregulation Circadian Rhythms Code Complex Data Diffuse Disease Drosophila genus Electrophysiology (science)Exhibits General Population Genetic Genetic Screening Grant Health Homologous Gene Human Image Individual Label Mammals Mediating Methods Molecular Na(+)-K(+)-Exchanging ATPase Names Neuroglia Neurons Neurosciences Research Pathway interactions Periodicity Physiological Processes Physiology Play Preparation Prevalence Process Productivity Proteins Regulation Role Signal Transduction Sleep Sleep Disorders Synapses System Techniques Testing Time Translating Work circadian circadian pacemaker experimental study fly gamma-Aminobutyric Acid genetic analysis improved insight integration site interdisciplinary approach knock-down neural circuit novel novel strategies novel therapeutics optogenetics pressure receptor sleep behavior sleep onset sleep quality sleep regulation suprachiasmatic nucleus tool

项目摘要

Many physiological processes and behaviors are under circadian clock control, including sleep. However, the molecular and circuit mechanisms underlying how the circadian clock regulates these behaviors remain poorly understood. We recently identified a novel molecule in Drosophila named WIDE AWAKE (WAKE) that plays a key role in mediating the circadian timing of sleep onset. In our original grant studying this molecule, we determined that WAKE is rhythmically expressed in arousal-promoting clock neurons and acts to upregulate GABAA receptors, thus cyclically suppressing the activity of these cells to promote sleep. Interestingly, growing evidence from our group and others suggests that WAKE-related molecules broadly function to spatially organize signaling complexes in a time-dependent manner. Moreover, there is a single homolog of WAKE in mammals, including humans, which is enriched in the circadian pacemaker suprachiasmatic nucleus. Thus, insights gained from studying WAKE in flies may help unravel how the circadian system regulates sleep in mammals as well. In this renewal of our previous grant, we propose to further our understanding of the mechanisms underlying the circadian modulation of sleep, by studying additional circuit and molecular mechanisms by which WAKE modulates this process. Specifically, we plan to carry out the following aims: 1) study the role of WAKE in regulating additional WAKE-expressing circadian clock neurons, and how this regulation impacts downstream arousal circuits; 2) identify and characterize additional proteins that interact with WAKE to modulate sleep; and 3) examine how glia may interact with these WAKE-expressing circadian clock circuits to regulate sleep. We will use a multidisciplinary approach, including cell biological, genetic, behavioral, and electrophysiological assays, to perform these studies. Circadian dysregulation of sleep is estimated to impact millions of people in the U.S. and has been implicated in adverse effects on health and productivity. Developing a better understanding of how the circadian clock regulates sleep could pave the way for identifying novel therapies to treat these disorders.

许多生理过程和行为都受到生物钟的控制，包括睡眠。然而,

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Branch-specific plasticity of a bifunctional dopamine circuit encodes protein hunger.

DOI：
10.1126/science.aal3245
发表时间：
2017-05-05
期刊：
Science (New York, N.Y.)
影响因子：
0
作者：
Liu Q;Tabuchi M;Liu S;Kodama L;Horiuchi W;Daniels J;Chiu L;Baldoni D;Wu MN
通讯作者：
Wu MN

Time for Bed: Genetic Mechanisms Mediating the Circadian Regulation of Sleep.

DOI：
10.1016/j.tig.2018.01.001
发表时间：
2018-05
期刊：
Trends in genetics : TIG
影响因子：
0
作者：
Blum ID;Bell B;Wu MN
通讯作者：
Wu MN

Clock-Generated Temporal Codes Determine Synaptic Plasticity to Control Sleep.

DOI：
10.1016/j.cell.2018.09.016
发表时间：
2018-11-15
期刊：
Cell
影响因子：
64.5
作者：
Tabuchi M;Monaco JD;Duan G;Bell B;Liu S;Liu Q;Zhang K;Wu MN
通讯作者：
Wu MN

Sleep interacts with aβ to modulate intrinsic neuronal excitability.

DOI：
10.1016/j.cub.2015.01.016
发表时间：
2015-03-16
期刊：
CURRENT BIOLOGY
影响因子：
9.2
作者：
Tabuchi, Masashi;Lone, Shahnaz R.;Liu, Sha;Liu, Qili;Zhang, Julia;Spira, Adam P.;Wu, Mark N.
通讯作者：
Wu, Mark N.

A Genetic Toolkit for Dissecting Dopamine Circuit Function in Drosophila.