Interdisciplinary Studies of Drosophila Rhythmic Behavior

果蝇节律行为的跨学科研究

基本信息

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
项目类别：
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

项目摘要

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.

我们之前的工作重点是果蝇的分子机制。最初在果蝇中表征的基因的直向同源物现已与脊椎动物（包括鱼类、青蛙、小鼠和人类）的节律行为和生理学的控制联系起来。在这里，我们对果蝇进行了四类跨学科研究。 (1) 我们将扩展经典的遗传筛选（化学诱变），以寻找导致异常活动/休息模式的突变。将确定受影响基因的身份、其表达的细胞和分子模式，并将开始对 2 号和 3 号染色体进行类似的筛选。 (2) 我们将表征一种新型的、睡眠减少的突变型失眠症患者。约 400 分钟/天，比野生型少近 9 小时。我们将确定 insomniac 在大脑中的表达位置、表达 insomniac 的细胞是否在组织睡眠中发挥其他作用，以及何时需要 insomniac 功能来确定睡眠持续时间 (3)。我们发现，当果蝇维持在光循环中时，mRNA 每天都会经历多聚腺苷酸化周期。我们将确定这些反应是否提供了新颖的作用。日长（季节性）测量机制。