核膜蛋白LBR调控昼夜节律的机理

昼夜节律存在于地球上几乎所有的生物内，并体现在各种生理过程与行为中。这些行为与生理过程的节律由体内的生物钟驱动。生物钟在分子水平的运作使得基因组的相当大一部分呈现出节律性表达，为行为与生理过程的节律提供了分子基础，然而对于这一调控过程的机理我们缺乏了解。近年的研究表明核膜蛋白从整体水平参与基因表达。申请人及同事发现内核膜组分核纤层蛋白B受体（Lamin B Receptor, LBR）在人的细胞系和果蝇内都参与生物钟的调控。本研究拟探讨LBR调控生物钟的机理，并检测LBR是否从整体水平参与生物钟的转录调控从而使转录组呈现出昼夜节律。本项目的研究结果将有助于了解生物钟如何调控行为与生理功能，从而利用昼夜节律辅助治疗，为当下逐渐被重视的时间治疗法（chronotherapy）提供理论依据。

Circadian rhythms exist in almost all organisms on the earth, and are manifest in various physiological processes and behavior. These rhythms are driven by endogenous circadian clocks. The actions of the clocks at the molecular level result in rhythmic expression of a significant portion of the genome, thus providing molecular basis for overt rhythms in behavior and physiology. However, we lack understanding regarding the underlying mechanism of this process. Studies in recent years have demonstrated a role for nuclear envelope in regulating global gene transcription. We found that an inner nuclear membrane component, lamin B receptor (LBR), participates in regulating the circadian clock both in human cell line and in Drosophila. Here we propose to investigate the mechanism of how LBR exerts effects on the clock. We will also test whether LBR is involved in global circadian transcription that leads to rhythmic expression of the transcriptome. Our study shall contribute to our understanding of how circadian clocks regulate rhythms in behavior and physiological processes. This will help facilitate development of drugs and therapies based on circadian rhythms, providing theoretical implications for the current growing interest in chronotherapy.