Post-translational control mechanisms of the circadian clock

生物钟的翻译后控制机制

• 批准号: 9115622
• 负责人: DAVID E SOMERS
• 金额: $ 31.14万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9115622
• 关键词: Address; Affect; Arabidopsis; Behavior; Biochemical; Biological; Biological Assay; Biological Models; Cell Cycle; Cell Nucleus; Cells; Chromatin; Circadian Rhythms; Clock protein; Complex; Cytosol; Defect; Developmental Process; Environment; Eukaryota; Feedback; Gatekeeping; Gene Expression; Gene Targeting; Genes; Genetic; Genomics; Goals; Health; Homodimerization; Hour; Human; Imaging Techniques; Individual; Intracellular Transport; Lead; Link; Mediating; Messenger RNA; Metabolism; MicroRNAs; Molecular; Movement; Mutate; Mutation; Nuclear; Nuclear Pore; Nuclear Pore Complex; Organism; Output; Pathway interactions; Peptide Hydrolases; Phase; Phenotype; Phosphorylation; Physiological Processes; Plant Model; Plants; Post-Transcriptional Regulation; Post-Translational Protein Processing; Process; Proteins; RNA Processing; Regulation; Regulatory Pathway; Role; Running; Series; Site; Slice; Small RNA; System; Temperature; Testing; Time; Yeasts; base; cellular imaging; circadian pacemaker; data mining; feeding; in vivo; mutant; novel; nucleocytoplasmic transport; plant growth/development; programs; tool; tumor metabolism; yeast two hybrid system

 DESCRIPTION (provided by applicant): Circadian rhythms are nearly ubiquitous endogenous timing systems that help coordinate the myriad physiological, metabolic and developmental processes that occur continuously in each organism at all times of the day. This circadian clock is comprised at the molecular level of interlocked and autoregulatory feedback loops that are built from complex interactions that are constantly changing in relation to each throughout the 24 hour cycle. The long term goal of this project is to understand the functional relationships among the post- transcriptional processes that keep the circadian oscillator running. We are using genetic, genomic, biochemical and cell biological tools and strategies of the model plant Arabidopsis to identify the molecules and mechanisms that regulate the transport of important proteins and mRNA between the cytosol and nucleus. We are focused in part on how a range of post-translational modifications of clock proteins affect both their positional and temporal intracellular localization. Gatekeeping features of the intracellular environment will also be addressed, both on a genomic scale and at the level of a single molecular species. We are applying for the first time in circadian studies single cell imaging techniques using a photo switchable fluorescent protein to assess features of clock protein movement and turnover that will be applicable to non-plant circadian systems. We are also exploiting certain plant-specific advantages of small RNA processing to address other post- transcriptional control mechanisms of the circadian clock. Taken together our program will probe mechanisms of circadian control that should be broadly applicable across all eukaryotic systems.

 描述（由申请人提供）：昼夜节律是几乎无处不在的内源性计时系统，有助于协调每个生物体在一天中的所有时间连续发生的无数生理、代谢和发育过程。这个生物钟由分子水平上的连锁和自动调节反馈回路组成，这些反馈回路是由复杂的相互作用构建的，这些相互作用在整个 24 小时周期中不断变化。该项目的长期目标是了解维持昼夜节律振荡器运行的转录后过程之间的功能关系。我们正在使用模式植物拟南芥的遗传、基因组、生化和细胞生物学工具和策略来识别调节重要蛋白质和 mRNA 在细胞质和细胞核之间运输的分子和机制。我们部分关注时钟蛋白的一系列翻译后修饰如何影响它们的位置和时间细胞内定位。细胞内环境的把关特征也将在基因组规模和单个分子物种水平上得到解决。我们首次在昼夜节律研究中应用单细胞成像技术，使用光可切换荧光蛋白来评估时钟蛋白运动和周转的特征，这将适用于非植物昼夜节律系统。我们还利用小RNA加工的某些植物特有优势来解决生物钟的其他转录后控制机制。总而言之，我们的计划将探讨昼夜节律控制机制，该机制应广泛适用于所有真核系统。