Interdisciplinary Studies of Drosophila Rhythmic Behavior

果蝇节律行为的跨学科研究

• 批准号: 7780899
• 负责人: Michael Warren Young
• 金额: $ 82.51万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-03 至 2012-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7780899
• 关键词: Adult; Advanced Sleep Phase Syndrome; Affect; Animals; Behavior; Biochemical; Biological; Biological Models; Brain; Cell Cycle Regulation; Cells; Chemicals; Chromosomes, Human, Pair 2; Chronic Insomnia; Circadian Rhythms; Clinical; Complex; Cues; Darkness; Dorsal; Drosophila genus; Exhibits; Exposure to; Fishes; Future; Genes; Genetic; Genetic Screening; Head; Hour; Human; Inborn Genetic Diseases; Interdisciplinary Study; Investigation; Length; Light; Link; Measurement; Messenger RNA; Mitotic; Molecular; Molecular Genetics; Molecular Profiling; Mus; Mutagenesis; Mutation; Narcolepsy; Nervous system structure; Nucleotides; Orthologous Gene; Pathway interactions; Pattern; Phase; Physiology; Poly A; Poly(A) Tail; Polyadenylation; Polyadenylation Pathway; Polynucleotide Adenylyltransferase; Population; Proteins; RNA Interference; Rana; Regulation; Rest; Role; Sleep; Sleep Apnea Syndromes; Sleep Disorders; System; Time; Ubiquitin; Vertebrates; Voltage-Gated Potassium Channel; Work; brain cell; casein kinase I; cdc Genes; circadian behavioral rhythms; circadian pacemaker; cryptochrome; day length; economic impact; fly; genome-wide; insight; mutant; novel; public health relevance; response; tool

Our prior work has focused on the molecular mechanisms underlying Drosophila¿s circadian rhythms. Orthologs of genes initially characterized in Drosophila have now been linked to the control of rhythmic behavior and physiology in vertebrates, including fish, frogs, mice and humans. Here we prose four classes of interdisciplinary investigations of the fly¿s rhythmic behavior. (1) We will extend a classical genetic screen (chemical mutagenesis) for mutations conferring aberrant activity/rest patterns. An X-chromosomal screen produced several mutant lines with effects on either sleep duration or phase. In future work, we will determine the identity of the affected genes, the cellular and molecular patterns of their expression, and will start a comparable screen on chromosomes 2 and 3. (2) We will characterize a novel, reduced- sleep mutant insomniac. These consistently rest for ~400 min/day, nearly 9 hours less than wild type. We will determine where insomniac is expressed within the brain, wheterh cells expressing insomniac have other roles in organizing sleep, and when insomniac function is required to determine sleep duration. (3) We have discovered that when Drosophila are maintained in a photocycle, period mRNA undergoes daily cycles of polyadenylation. The time of polyadenylation can be delayed by prolonged exposure to light. We will determine whether these responses provide a novel mechanism for day- length (seasonal) measurement.

我们先前的工作主要集中在果蝇昼夜节律的分子机制上。 最初在果蝇中表征的基因的直系同源物现在已经与脊椎动物（包括鱼、青蛙、小鼠和人类）的节律行为和生理学的控制相关联。 在这里，我们散文四类跨学科的调查苍蝇的节奏行为。 (1)我们将扩展一个经典的遗传筛选（化学诱变）的突变赋予异常的活动/休息模式。 X染色体筛选产生了几个对睡眠持续时间或睡眠阶段有影响的突变株系。 在未来的工作中，我们将确定受影响的基因的身份，其表达的细胞和分子模式，并将在2号和3号染色体上开始一个可比较的筛选。 (2)我们将描述一个新的，睡眠减少的失眠症患者。 这些持续休息约400分钟/天，比野生型少近9小时。 我们将确定失眠症在大脑中的何处表达，表达失眠症的细胞是否在组织睡眠中发挥其他作用，以及何时需要失眠症功能来确定睡眠持续时间。 (3)我们已经发现，当果蝇维持在一个光周期中时，周期mRNA经历每天的多聚腺苷酸化循环。 多聚腺苷酸化的时间可以通过长时间暴露于光而延迟。 我们将确定这些反应是否提供了一个新的机制，日长（季节）测量。