Molecular and Cellular Mechanisms of Biological Rhythms

从地球上的原核生物到真核生物，几乎所有生物体内都有生物钟产生的昼夜节律。尽管昼夜节律的特性对所有生物都是共同的，但昼夜节律的分子机制是否普遍存在于生物体中尚不清楚。在这项联合研究中，日本和美国的研究人员合作阐明了生物钟的分子和细胞基础，系统地研究了从原核生物到哺乳动物的生物钟。在过去的2年中，日本和美国的研究小组在蓝藻、果蝇和小鼠等中独立分离出了几个时钟基因。特别值得注意的是，一个哺乳动物的果蝇基因同源物和一个哺乳动物的时钟基因同源物以及编码与Clock蛋白异二聚化的蛋白质的BMAL1基因已经被克隆出来，这表明生物钟成分至少在动物界是共同的。此外，尽管原核生物的昼夜节律分子可能不同，但我们已经证明，所有生物的昼夜节律都是由正反馈和负反馈的转录/翻译机制产生的，这表明蝉振荡是基于普遍的分子机制。此外，我们在以下问题上取得了优异的成绩：松果体光色素（pinopsin），从视交叉上核接收的单细胞，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.