Department of Physiology and Systems Bioscience
What is Circadian Rhythm, for humans and all living organisms? This is our main question. Discrepancies between environmental time and the body clock is known to disrupt circadian rhythms and affect our health in various ways. The study of circadian rhythms including emergence, maintenance, and misalignment, will lead to the understanding of the mechanisms of disease development caused by certain environmental factors. We aim to elucidate the principles and solve social problems by considering the elaborate and flexible circadian rhythm, which controls environmental adaptation and temporal order to maintain our homeostasis.
01Biological clock and circadian rhythm
We have recently clarified that the biological clock is not present in pluripotent stem cells such as ES cells and iPS cells, but is formed in conjunction with development and cell differentiation (PNAS, 2010). In addition, it was found that the formation of the biological clock is accompanied by synchronous adaptation to the environmental rhythms of the outside world (maternal rhythms) (PNAS, 2017). These findings suggest that the circadian clock is an interface between the external environment and the internal physiology of the body. In other words, the body clock is a physiological function that creates time order in the body in relation to the environment, and is the basic principle of the operating system of life. Interestingly, we observed the transition of two different types of rhythms during the developmental process, from segmentation clock to circadian clock (PNAS, 2022). During somitogenesis, circadian clock-mediated 24-hour temporal order is likely to be suppressed not to allow it to interfere with the segmentation clock. Our goal is to elucidate the biological control system based on the biological clock from the understanding of the principle of the circadian rhythm and the control mechanism of homeo-dynamics that penetrates the hierarchy of molecular, cellular, tissue, organ, and individual levels.
02Circadian rhythm disorder as pre-symptomatic disease
However, simply telling people to live a regular life or to go to bed early and wake up early is not a solution to the social problem. Essential workers are indispensable for a safe and comfortable society. How do environmental factors, such as deviations in lifestyle and body clocks, affect the physiological functions and cause changes in molecular mechanisms at the cellular level? Research on the mechanism of homeostasis disruption due to environmental factors is currently an uncharted field with little progress due to the barrier of individual differences. We are challenging this difficult scientific question with new approaches. Recently, we succeeded in developing a new approach named "mouse cohort model" to deduce the process of circadian disorders. Using this, we showed that the circadian misalignment resulted in deleterious consequences in mice (Sci Rep, 2020). The environmental perturbation disrupting circadian temporal order severely impairs homeostasis. We are now working to answer the question of how the environmental perturbation induces the sequence of circadian disorders.
03Human circadian physiology: From Lab to Society
Publication List (Selected)