Interdisciplinary studies of the Drosophila Circadian Clock

果蝇昼夜节律钟的跨学科研究

• 批准号: 7354090
• 负责人: Michael Warren Young
• 金额: $ 36.92万
• 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 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7354090
• 关键词: Affect; Amino Acids; Area; Behavior; Behavioral; Binding; Biochemical Genetics; Biological Models; Chloride Anion Exchanger; Circadian Rhythms; Class; Daily; Data; Depth; Development; Drosophila genus; Elements; Fishes; Flavins; Gene Expression; Gene Proteins; Genes; Genome; Glycogen Synthase Kinase 3; Head; Homologous Gene; Human; Individual; Interdisciplinary Study; Investigation; Lethal Genes; Life; Light; Link; Maps; Molecular; Mus; Mutation; Mutation Analysis; Orthologous Gene; Output; Periodicity; Phosphorylation; Physiological; Physiology; Protein Splicing; Proteins; Protocols documentation; Rana; Recovery; Reporting; Research; Role; SLC26A3 gene; Series; Structure; Techniques; Tissues; Vertebrates; Work; base; chemical genetics; circadian behavioral rhythms; circadian pacemaker; fly; insight; interest; novel; null mutation; programs; protein function; research study; response

We have been studying the molecular control of circadian behavioral rhythms using Drosophila as a model system. Orthologs of genes initially characterized in the fly,have now been linked to the control of rhythmic behavior and physiology in vertebrates, including fish, frogs, mice and humans. Here we propose three classes of interdisciplinary investigations of the Drosophila clock. (1) We will conduct collaborative structural studies that can help us determine how specific regulatory actions, previously recognized genetically and biochemically, are performed by certain domains of the PER protein. Does the structure of PER indicate how it interacts with TIM and DBT? Do such data suggest how TIM suppresses PER's phosphorylation by DBT? Does a putative LOV domain near the N-terminus of PER possess a flavin binding domain? (2) We will generate new mutations for the analysis of vital clock genes by Conditional Protein Splicing. Our studies of hyper- and hypo-morphic mutations of GSK-3, dbt, vri, and Pdp-1 indicate that each is a key component of the Drosophila clock. However, because null mutations of these genes are lethal, it has been difficult to determine their full effects on the clock. We are developing a form of chemical genetics in which small diffusible molecules will reversibly control the presence of each vital protein in living flies. (3) We will produce new microarray and statistical approaches to clarify features of rhythmic genome activity and to determine if flies use a single molecular mechanism to generate all circadian rhythms. To begin to link the clock to specific behavioral and physiological outputs, we will investigate a novel set of genes that are regulated by a paired action of light and the circadian clock.

我们一直在研究使用果蝇作为模型的昼夜节律节奏的分子控制 系统。最初以苍蝇为特征的基因的直系同源物已与节奏的控制有关 脊椎动物的行为和生理学，包括鱼，青蛙，小鼠和人类。在这里我们提出三个 果蝇时钟的跨学科研究类别。 （1）我们将进行协作结构 可以帮助我们确定以前在遗传和 从生化上，由每蛋白的某些结构域进行。每个人的结构是否表示如何 它与Tim和DBT互动吗？这样的数据是否表明TIM如何抑制DBT的人均磷酸化？ 在每个人的N末端附近的假定LOV域是否具有黄素结合域？ （2）我们会的 通过条件蛋白剪接生成新的突变，以分析生命时钟基因。我们的研究 GSK-3，DBT，VRI和PDP-1的超形和倍形突变表明，每个突变都是每个突变 果蝇时钟。但是，由于这些基因的无效突变是致命的，因此很难 确定它们对时钟的全部影响。我们正在开发一种化学遗传学形式，其中很小 扩散的分子将可逆地控制生物中每个重要蛋白的存在。 （3）我们将生产 新的微阵列和统计方法阐明节奏基因组活性的特征，并确定是否是否 苍蝇使用单个分子机制产生所有昼夜节律。开始将时钟链接到 特定的行为和生理输出，我们将研究一组由A调节的新型基因 光的动作和昼夜节律的动作。