CLOCK MECHANISM UNDERLYING RHYTHMIC BEHAVIOR

描述（来自申请人的摘要）：本项目的长期研究目标是从分子角度描述果蝇昼夜节律振荡器的特征。该实验室以前的研究表明，PER和TIM蛋白在体内相互作用，这种复合物对光的反应是解离的。他们还表明，细胞质PER-TIM复合物的破坏与PER磷酸化和PER核进入的延迟有关。本申请的具体目的是：（1）表征参与per mRNA水平的转录后控制的反式作用因子和顺式作用元件，（2）确定PER、TIM和dCLOCK磷酸化的作用并鉴定PER和TIM的体内配偶体，和（3）表征dCLOCK表达的空间和时间调节，并确定PER和TIM如何与dCLOCK-CYC复合物相互作用。

DESCRIPTION (from applicant's abstract): The long-term research objective of this project is to characterize, in molecular terms, the circadian oscillator of Drosophila. Previous studies from this laboratory have shown that PER and TIM proteins interact in vivo and that this complex disassociates in response to light. They have also shown that the disruption of the cytoplasmic PER-TIM complex is associated with a delay in PER phosphorylation and PER nuclear entry. The specific aims of this current application are to: (1) Characterize trans-acting factors and cis-acting elements that participate in the post-transcriptional control of per mRNA levels, (2) Determine the role of PER, TIM and dCLOCK phosphorylation and identify in vivo partners of PER and TIM, and (3) Characterize the spatial and temporal regulation of dCLOCK expression and determine how PER and TIM interact with the dCLOCK-CYC complex.