Molecular and Cellular Mechanisms of Biological Rhythms

由内部生物钟产生的昼夜节律在地球上几乎所有的生物体（从原核生物到真核生物）中都可以观察到。虽然昼夜节律的特性对所有生物体都是共同的，但昼夜节律的分子机制是否在生物体中普遍存在还不清楚。在这项联合研究中，日本和美国的研究人员相互合作，阐明生物钟的分子和细胞基础，从原核生物到哺乳动物进行系统研究。在过去的2年中，日本和美国的研究小组分别从蓝藻、果蝇和小鼠等中分离出了几个时钟基因，特别值得注意的是，已经克隆了果蝇per基因的哺乳动物同源物和哺乳动物Clock基因的果蝇同源物以及编码与CLOCK蛋白异源二聚化的蛋白质的BMAL 1基因，这表明生物钟的组成部分至少在动物界是普遍的。此外，虽然在原核生物的昼夜节律分子可能是不同的，我们已经表明，昼夜节律是由一个积极的和消极的反馈转录/翻译机制在所有的生物体和蝉振荡是基于普遍的分子机制。此外，我们还在以下几个方面取得了优异的结果：松果体色素（pinopsin），视交叉上核的单细胞记录，星形胶质细胞在昼夜节律中的作用，心律失常突变小鼠的分离和ICER在昼夜节律钟中的作用。

Circadian rhythms generated by an internal biological clock are observed in almost all the organisms from prokaryotes to eukaryotes living on earth. Although the properties of circadian rhythms are common to all of the organisms, it is unknown if the molecular mechanisms of the circadian rhythm is ubiquitous to the organisms. In this joint research, Japanese and US researchers collaborated with each other in elucidating molecular and cellular basis of circadian clock, investigating systematically from prokaryotes to mammals. During the past 2 years, Japanese and US group have independently isolated several clock genes in cyanobacteria, Drosophila and mice and so on. Particularly, it is remarkable that a mammalian homolog of the Drosophila per gene and a Drosophila homologs of mammalia Clock gene and BMAL1 gene encoding a protein heterodimerized with CLOCK protein have been cloned, suggesting that the circadian clock components are common at least to the animal kingdom. In addition, although the circadian molecule in prokaryotes may be different, we have shown that the circadian rhythm is generated by a positive and negative feedback transcription/translation mechanisms in all the organisms and suggest that cicadian oscillation is based on universal molecular mechanisms. Moreover, we have obtained excellent results in the following issues ; the pineal photopigment (pinopsin), single cell recorging from the suprachiasmatic nucleus, the role of astrocyte in circadian rhythm, isolation of arrhythrnic mutant mice and the role of ICER in the circadian clock.