BIOLOGICAL CLOCKS--GENES, BEHAVIOR AND NEUROBIOLOGY

生物钟——基因、行为和神经生物学

• 批准号: 6107520
• 负责人: JEFFREY C HALL
• 金额: $ 17.27万
• 依托单位: BRANDEIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-01 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6107520
• 关键词: Drosophilidae; behavioral /social science research tag; behavioral genetics; biological clocks; biological signal transduction; chimeric proteins; circadian rhythms; cyclic AMP; developmental genetics; developmental neurobiology; ethology; fusion gene; gene expression; gene mutation; genetically modified animals; immunocytochemistry; laboratory rabbit; molecular cloning; molecular genetics; neuroanatomy; neurohormones; photobiology; site directed mutagenesis

Circadian rhythms are organismically ubiquitous biological cycles whose propr daily regulation is strongly connected to the well being of species ranging from microbes to mammals. The 25- year-old genetic approach toward understanding these rhythms has recently begun to reveal elements of the clock mechanisms that underlie daily rhythmicities. This sub-proposal in a Program Project application revolves around the behavioral genetic, neuro- genetics, and molecular neurobiology of circadian rhythms in Drosophila. The experiments proposed stress more of a ~systems~ approach than one that would concentrate upon the hard core of molecular pacemaking. Thus, the neural substrates of behavioral rhythms, and a periodic feature of late development, will be delved into by application of rhythm mutants and transgenic strains carrying manipulated forms of clock-genes; these studies include descriptions of anatomic output pathways from neurons that are candidate for CNS-pacemaker cells, and selectively effected perturbations of the structure and function of such cells in conjunction with bioassaying the effects of the molecularly mediated neuronal damage. Input paths to the central pacemakers, which bring in environmental cues to effect crucial daily re-sets of the clock, will be dissected both in terms of anatomy and elements of signal-transduction pathways that putatively participate in processing the resetting stimuli. Output pathways will be investigated, with respect to varying physiological parameters that are hypothesize to be the first- or second-stage targets of clock- gene functions. The latter includes cyclically varying levels of the encoded mRNAs and proteins; these molecular cyclings will be tracked in conjunction with physiological recordings and perturbations, by applying a transgene in which portions of a clock gene (called period) have been fused to DNA sequences encoding a real-time reporter; this is luciferase activity, which as recently been shown to permit non-invasive monitoring of molecular rhythms in live adult flies and in per-expressing tissues explanted from animals late in development. Genetic and molecular-genetic studies are proposed in two areas: (1) analysis of the behavioral and neurobiological consequences of manipulating a clock-controlled gene~s expression, and of effecting the same kinds of perturbations of a neuropeptide-encoding gene whose product is co-expressed with clock genes in a subset of the CNA pacemaking neurons; (2) genetic and biological studies of rhythm mutants, recently isolated on the basis of defects in circadian behavioral rhythms: these phenogenetic studies will proceed into cloning of the genes defined by mutations that appear to be the most promising candidates for disrupting important elements of Drosophila~s circadian system.

昼夜节律是生物体普遍存在的生物周期