Characterization of Sleep Mutants of Drososphila

果蝇睡眠突变体的表征

• 批准号: 7474542
• 负责人: Chiara Cirelli
• 金额: $ 24.03万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7474542
• 关键词: Affect; Age; Aging; Arousal; Behavior; Biological; Biological Models; Brain; Chromosomes, Human, Pair 1; Circadian Rhythms; Code; Complex; Daily; Data; Development; Drosophila genus; Drosophila melanogaster; Excision; Female; Gene Expression; Gene Mutation; Genes; Genetic; Genetic Screening; Genome; Genomics; Head; Health; Hour; Human; In Situ Hybridization; Laboratories; Light; Link; Longevity; Mammals; Memory; Molecular; Molecular Genetics; Molecular Profiling; Motor Activity; Mus; Mutagenesis; Mutation; Numbers; Pathway interactions; Pattern; Performance; Phenotype; Phosphorus; Physiological; Principal Investigator; Protein Overexpression; Proteins; Quantitative Trait Loci; RNA Interference; Recovery; Regulation; Relative (related person); Reporting; Research; Screening procedure; Sequence Homology; Sleep; Sleep Deprivation; Standards of Weights and Measures; Stress; Testing; Time; Transgenic Organisms; Wakefulness; Western Blotting; base; brain electrical activity; circadian pacemaker; day; fly; gain of function mutation; hypnotic; interest; loss of function mutation; mutant; novel; programs; response; sleep regulation; vigilance

DESCRIPTION (provided by applicant): Sleep is present in all species where it has been studied, but its functions remain unknown. A sufficient amount of sleep constitutes a fundamental biological need. For example, curtailing the amount of sleep in normal sleepers affects performance, vigilance, memory and health. Like all complex behaviors, sleep is both environmentally modulated and genetically determined. However, the responsible genes have not been discovered. To identify them, we have initiated a genetic screening for short sleepers in the fruit fly Drosophila melanogaster. Mutagenesis screening in Drosophila has helped unraveling cellular mechanisms that are highly conserved across species, e.g. those controlling development, aging, stress memory, and circadian rhythms. Over the past few years, our laboratory and others have shown that fly sleep shares many key features with mammalian sleep. As in mammals, sleep in Drosophila is characterized by increased arousal thresholds and by changes in brain electrical activity. Fly sleep is regulated independent of the circadian clock, is modulated by stimulants and hypnotics, and is affected by age. Also, fly sleep is associated with changes in brain gene expression similar to those observed in mammals. Over the past 3 years, we have screened approximately 8000 mutant lines, most of which carry single-gene mutations. We found that the amount and regulation of sleep are highly conserved: almost all flies sleep between 400 and 800 min/24 hours and show increased sleep duration and continuity after sleep deprivation. We have also identified several short sleeper lines, three of which are particularly interesting. Despite the reduced amount of sleep (<230 min/day), these lines show normal day-time performance and vigilance. When sleep deprived, they recover most of the sleep lost, suggesting that it is biologically important. The short sleep mutation is due to the genomic insertion of a P element whose mobilization reverts them to normal sleep, suggesting a single gene effect. We propose to characterize these three lines genetically, molecularly, and behaviorally. We will manipulate the expression of the genes responsible for the short sleep phenotype, investigate the molecular pathways controlled by these genes, and characterize their impact on performance, memory, circadian rhythms and life span. This research will help to identify the molecular mechanisms regulating the need for sleep and provide novel clues to its functions.

描述（由申请人提供）：在所有研究的物种中都存在睡眠，但其功能仍然未知。足够的睡眠构成了基本的生物学需求。例如，减少正常睡眠者的睡眠量会影响表现，警惕，记忆和健康。像所有复杂行为一样，睡眠既是环境调节又有遗传确定的。但是，尚未发现负责的基因。为了识别它们，我们已经开始了果蝇果蝇中短卧铺的基因筛查。果蝇中的诱变筛查有助于揭开在物种之间高度保守的细胞机制，例如那些控制发展，衰老，压力记忆和昼夜节律的人。在过去的几年中，我们的实验室和其他人表明，Fly Sleep与哺乳动物睡眠有许多关键特征。与哺乳动物一样，果蝇中的睡眠的特征是唤醒阈值增加和脑电活动的变化。苍蝇睡眠的调节是独立于昼夜节律时钟的调节，受兴奋剂和催眠剂的调节，并受年龄的影响。同样，苍蝇睡眠与类似于哺乳动物观察到的脑基因表达的变化有关。在过去的3年中，我们筛选了大约8000个突变线，其中大多数携带单基因突变。我们发现睡眠的数量和调节是高度保守的：几乎所有的苍蝇睡眠在400到800分钟/24小时之间，并显示出睡眠不足后的睡眠持续时间和连续性增加。我们还确定了几条短的卧铺线条，其中三条特别有趣。尽管睡眠量减少（<230分钟/天），但这些线条表现出正常的日常表现和警惕。当睡眠被剥夺时，他们会恢复大部分睡眠丧失，这表明它在生物学上很重要。短睡眠突变是由于P元素的基因组插入，该P元素的动员使它们恢复到正常的睡眠，这表明单一基因效应。我们建议以遗传，分子和行为表征这三条线。我们将操纵负责短睡眠表型的基因的表达，研究由这些基因控制的分子途径，并表征它们对性能，记忆，昼夜节律节奏和寿命的影响。这项研究将有助于确定调节睡眠需求的分子机制，并为其功能提供新的线索。