生物节律与精神疾病的关系非常密切，破坏生物节律会增加罹患多种精神疾病的风险，精神疾病患者常伴随有昼夜节律紊乱，二者之间相互作用的分子机制仍不清楚。申请人在果蝇中筛选了多个与精神疾病相关基因的同源基因，首次发现一个与双相情感障碍相关的基因Ank2参与果蝇活动节律的调节。敲低Ank2显著降低果蝇活动的节律性和延长果蝇活动节律周期；进一步研究发现敲低Ank2显著降低核心生物钟基因period的mRNA和蛋白水平，并显著降低period的前体mRNA水平。由此我们推测：Ank2可能通过影响period的转录来调节果蝇生物节律。基于前期研究基础，本项目拟继续在行为、组织、细胞和分子水平研究Ank2在果蝇生物节律调控过程中的功能及分子机制。本项目的研究结果将有助于挖掘新的调控生物钟的基因，丰富和完善生物钟调控的机理，对揭示生物钟与精神疾病之间的关系具有重要意义，为临床上的“时间疗法”提供理论依据。

Psychiatric disorders are closely connected with circadian rhythms, perturbations in circadian rhythms increase the risk of psychiatric disorders and psychiatric diseases are often accompanied by circadian disruptions, but the molecular underpinnings remain largely unclear. We screened homologous genes that have been previously reported to be associated with psychiatric diseases and first found that Ank2, a gene associated with bipolar disorder, is involved in circadian rhythm regulation. Knocking down Ank2 leads to attenuated the rhythmicity and lengthened period of locomotor rhythms in flies. Furthermore, we found that knocking down Ank2 decrease mRNA and protein levels of core clock gene period. Knocking down Ank2 also decreased the pre-per mRNA level. We speculate Ank2 regulate Drosophila circadian clock through promoting the transcription of per. This study intends to further explore the function and molecular mechanism of Ank2 in regulating circadian clock at behavioral, tissue, cellular, and molecular levels. Our results will help excavate the new genes in regulating circadian clock, enriching and improving the molecular mechanism of circadian clock. It is of great significance to reveal the relationship between circadian clock and psychiatric disorders, this will provide theoretical foundation for clinical time therapy.