COORDINATION OF CIRCADIAN PHYSIOLOGY OF DIVERSE SPECIES

调节日常生活和日常行为、生理和生物化学规律的生物钟是生物组织的基本属性。近年来，在阐明时钟结构的解剖定位、时钟功能的生理学以及昼夜节律性背后的生化/分子事件方面取得了长足的进步。这些进展是在不同的生物体中取得的，它们具有许多共同的形式和分子特性，但在理解时钟和发挥功能的水平上有所不同。在研究得最好的模型系统中，有蓝藻聚球藻、丝状真菌粗糙脉孢霉、有效松果腺和哺乳动物视交叉上核(SCN)，它们都提供了一个非常大的、复杂的谜题的不同部分。然而，关于时钟输入、振荡和输出的完整图景并不明显，因为不同的系统提供了不同的观点。这可能是由于实验系统和/或不同方法的真正生物学差异造成的。本计划项目资助结合了4个已建立的实验室的努力，这些实验室有合作教育和研究的历史，致力于这些充分研究的模型系统中生物钟功能的不同方面。欧内斯特博士(项目2)将在一种独特的从大鼠SCN衍生的永生化细胞系中研究昼夜节律振荡的机制及其输出。Bell-Pedersen博士(项目3)将探索脉孢子菌的发育和代谢过程与昼夜节律功能的关系。V.M.Cassone博士(项目4)将研究小鸡松果体中节律的产生和与褪黑素生物合成的偶联的分子机制，以及培养的胶质细胞中褪黑素作用的细胞机制。两个技术核心和一个管理/整合核心将使每个实验室能够扩展其自身研究的边界：1)由T.Thomas博士指导的基因组学(核心A)将进行现代基因组分析，包括高密度转录图谱、DNA微阵列技术和EST分析。2)由Mark Zoran博士指导的细胞生理学/成像核心(Core B)将对基因表达进行电生理和实时成像。3)由Cassone博士领导的管理和综合核心(Core C)将保持记录，通过安排管理会议促进实验室之间的互动，并协调与咨询委员会的会议。此外，该矿石将有助于对所有实验室收集的整个数据集进行数据分析，汇编序列和功能数据，将这些数据存档，并分析这些不同系统之间的系统发育关系。所有四个项目都通过对不同生物系统的共同技术方法以及对生物时钟功能的跨学科、比较分析的承诺而联系在一起。

The biological clocks that regulator daily and circadian patterns of daily behavior, physiology and biochemistry are fundamental properties of biological organization. In recent years, great strides have been made in elucidating the anatomical localization of clock structures, the physiology of clock function and the biochemical/molecular events underlying circadian rhythmicity. These advances have been made in diverse organisms, which share many common formal and molecular properties but which differ in the level at which clocks are understood and at which they function. Among the best-studied model systems are the cyanobacterium Synechococcus sp., the filamentous fungus Neurospora crassa, the avail pineal gland and the mammalian suprachiasmatic nucleus (SCN), which have all provided disparate pieces of a very large, complex puzzle. However, a complete picture of this puzzle, of clock input, oscillation and output, is not apparent, because divergent systems provide dissimilar views. This may be due to real biological differences in experimental systems and/or diverse approaches. The present Program Project Grant combines the efforts of 4 established laboratories, which have a history of cooperative education and research, devoted to different aspects of biological clock function in these well-studied model systems. Dr. D.J Earnest (Project #2) will investigate mechanisms of circadian oscillation and its output in a unique immortalized cell line derived from the rat SCN. Dr. D. Bell-Pedersen (Project #3) will explore the relationship of developmental and metabolic processes with circadian rhythm function in Neurospora. Dr. V.M. Cassone (Project #4) will study the molecular mechanisms of rhythm generation and coupling to melatonin biosynthesis in the chick pineal and of cellular mechanisms of melatonin action in cultured glia. Two Technical Cores and an Administrative/Integrative Core will enable will enable each laboratory to extend the boundaries of their own research: 1) The Genomics (Core A), directed by Dr. T. Thomas, will perform modern genomics analyses including high density transcriptional profiling, DNA microarray technology and EST analyses. 2) The Cell Physiology/Imaging Core (Core B), directed by Dr. Mark Zoran, will perform electrophysiological and real-time imaging of gene expression. 3) The Administrative and Integrative Core (Core C), directed by Dr. Cassone, will maintain records, facilitate interaction of laboratories by scheduling of regulate meetings, and coordinate meetings with advisory committees. In addition, this ore will facilitate data analysis of the entire data set collected by all laboratories compiling sequence and functional data, archiving these data and analyzing phylogenetic relationships among these diverse systems. All four projects are bonded by common technological approaches to diverse biological systems and by a commitment to interdisciplinary, comparative analyses of biological clock function.