Molecular and Cellular Mechanisms of Biological Rhythms

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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.