生物钟是以大约24小时为周期的生物节律，其作用机制是由相互作用的正负转录反馈环路所驱动的。它在生物体的生理、代谢和行为活动中起重要作用。Groucho (Gro)/Transducin-like Enhance of split (TLE)蛋白是在进化上保守的、广泛表达的一种共抑制因子。Gro/TLE蛋白与多个信号通路相互作用来调控转录，如Notch、Wnt和BMP，它在动物的生长发育及人类疾病起重要作用。然而，Gro/TLE蛋白对生物钟的作用还未有报道。我们前期结果发现，斑马鱼gro1和2表现为24小时的振荡周期，受生物钟的直接调控。另外，突变gro1和2影响斑马鱼生物钟基因的表达及运动节律。因此，本项目将利用斑马鱼为模式动物，采用多钟遗传学手段，如基因敲除、过表达和化学遗传学，深入研究Gro1和2在斑马鱼生物钟的功能以及作用机制，为生物钟分子机制的研究提供更深入的理解。

The circadian clock is endogenous oscillations generated by an interlocking positive and negative transcriptional/translational feedback loop, with a period of approximately 24 hours in all organisms. It plays an important role in regulating physiology, metabolism and behavior in organisms. Groucho (Gro)/Transducin-like Enhance of split (TLE) protein is a conserved and broadly expressed corepressor. Gro/TLE proteins regulate transcription in several signaling pathways including Notch, Wnt and BMP, playing critical roles in organism development and human diseases. However, its role in circadian regulation has not been reported so far. In our prophase data, we found zebrafish gro1 and gro2 are rhythmically expressed and directly regulated by the circadian clock through E-box. Furthermore, zebrafish gro1 and gro2 mutants show disturbed expression of clock genes and behavior rhythms. Therefore, in this study, we will use zebrafish as model organism, employing multiple genetic tools such as CRSIPR/Cas9, transgenic techniques and chemical genetics, to investigate the mechanisms underlying the regulation of Gro1 and Gro2 in the circadian clock. These will provide our further understanding of the molecular mechanisms of the circadian clock.