Genetic and Molecular Dissection of the Neurospora Clock

脉孢菌钟的遗传和分子解剖

• 批准号: 8076349
• 负责人: Jay C. Dunlap
• 金额: $ 70.88万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-02-01 至 2012-08-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8076349
• 关键词: Affect; Animals; Biochemistry; Biological; Biological Clocks; Biological Models; Cells; Characteristics; Circadian Rhythms; Clock protein; Collaborations; Complex; Core Protein; DNA; Data; Dissection; Engineering; Environment; Epitopes; Eukaryotic Cell; Event; Feedback; Financial compensation; Gene Expression; Genes; Genetic; Genome; Genomics; Goals; Homologous Gene; Human; Informal Social Control; Investments; Knowledge; Language; Light; Logic; Mental Health; Mental Processes; Mental disorders; Metabolism; Modeling; Modification; Molecular; Molecular Genetics; Mutagenesis; Neurospora; Organism; Output; Pathway interactions; Phosphorylation; Phosphorylation Site; Phosphotransferases; Physiological Processes; Physiology; Post-Translational Protein Processing; Prevention; Production; Property; Proteins; Proteomics; Reagent; Regulation; Research Infrastructure; Resources; Rest; Route; Series; Site; Sleep; Stable Isotope Labeling; Staging; Structure; System; Techniques; Temperature; Testing; Time; Work; analog; base; casein kinase II; cell behavior; chromatin immunoprecipitation; circadian pacemaker; design; gene replacement; mutant; novel; operation; physical conditioning; promoter; protein protein interaction; public health relevance; response; synthetic biology; tool

DESCRIPTION (provided by applicant): Virtually all eukaryotic organisms appropriately examined have been shown to possess the capacity for endogenous temporal control and organization known as a circadian rhythm. The cellular machinery responsible for generating rhythms is collectively known as the biological clock. A healthy circadian clock underlies both physical and mental health. Because of the ubiquity of its influence on human mental and physiological processes - from circadian changes in basic human physiology to the clear involvement of rhythms in work/rest cycles and sleep - understanding the clock is basic to prevention and treatment of many physical and mental illnesses. Our specific aims are designed to further our understanding of the means through which the clock generates biological time. Post-translational modification, chiefly phosphorylation, of clock proteins is central to their function. Specific Aim #1 is focused on the complete identification of phosphorylation sites in clock proteins, how they change with time, and how this impacts the proteins' activities. Specific Aim #2 focuses on understanding the dynamics of the oscillator, how it achieves temperature compensation, and the molecular details of how the parts interact. Efforts to reconstruct the oscillator will continue. Specific Aim #3 builds upon our strong grounding in genomics and genetics which we will harness to identify novel components required for oscillator function and determine the means through which they act. Our long term goals are to describe, in the language of genetics and biochemistry, the feedback cycle comprising the circadian clock, how this cycle is synchronized with the environment, and how time information generated by the feedback cycle is used to regulate the behavior of cells and organisms. These projects are complementary and mutually enriching in that they rely on genetic and molecular techniques to dissect, and ultimately to understand, the organization of the cell as a function of time. PUBLIC HEALTH RELEVANCE: Virtually all eukaryotic organisms appropriately examined have been shown to possess the capacity for endogenous temporal control and organization known as a circadian rhythm, the output of a biological clock. A healthy circadian clock underlies both physical and mental health. Because of the ubiquity of its influence on human mental and physiological processes - from circadian changes in basic human physiology to the clear involvement of rhythms in work/rest cycles and sleep - understanding the clock is basic to prevention and treatment of many physical and mental illnesses.

描述（由申请人提供）：实际上，经过适当检查的所有真核生物都具有内源性时间控制的能力和被称为昼夜节律的组织。负责产生节奏的细胞机制统称为生物钟。健康的昼夜节律是身心健康的基础。由于其对人类心理和生理过程的影响无处不在 - 从基本人类生理学的昼夜节律到明显的节奏参与工作/休息周期和睡眠 - 了解时钟是预防和治疗许多身体和精神疾病的基础。我们的特定目标旨在进一步了解时钟产生生物学时间的手段。时钟蛋白的翻译后修饰（主要是磷酸化）是其功能的核心。特定的目标＃1集中于对时钟蛋白中磷酸化位点的完整鉴定，它们如何随时间变化以及如何影响蛋白质的活性。特定目标＃2专注于理解振荡器的动力学，如何实现温度补偿以及零件如何相互作用的分子细节。重建振荡器的努力将继续。特定目的＃3建立在我们在基因组学和遗传学方面的强大基础上，我们将利用这些基础，以确定振荡器功能所需的新成分并确定其作用的手段。我们的长期目标是用遗传学和生物化学的语言描述包含昼夜节律时钟的反馈周期，该周期如何与环境同步，以及如何使用反馈周期产生的时间信息来调节细胞和生物体的行为。这些项目是互补的和相互丰富的，因为它们依赖于遗传和分子技术来剖析细胞作为时间的函数，并最终理解细胞的组织。 公共卫生相关性：几乎所有经过适当研究的真核生物都具有内源性时间控制和组织的能力，被称为昼夜节律，即生物钟的输出。健康的昼夜节律是身心健康的基础。由于其对人类心理和生理过程的影响无处不在 - 从基本人类生理学的昼夜节律到明显的节奏参与工作/休息周期和睡眠 - 了解时钟是预防和治疗许多身体和精神疾病的基础。