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.

我们一直在研究以果蝇为模型的昼夜行为节律的分子控制