Just as warblers sing and swallows migrate in spring, animal activities, such as migration, hibernation, and reproduction, are repeated annually. Seasonal changes in animal behavior were described by the Greek philosopher Aristotle in his “Animalia Historium” in the 300s B.C. However, the mechanism by which living organisms adapt to the changes of the four seasons using a “circannual clock” that keeps a rhythm of approximately one year remains undefined over 2,000 years later. We aim to unravel this long-standing mystery by focusing on unique animals such as medaka fish and Japanese quail, mice, rhesus monkeys, and humans. The regulation of reproductive activity is linked to food production. Further, various human diseases, such as heart disease, influenza, and mental illness, are more severe in winter, and mortality rates are consequently higher than those during other seasons. Therefore, we aim to improve food production and human health by understanding the mechanisms by which animals sense and adapt to seasonal changes.

　　Corals and sea turtles are known to lay their eggs during full and/or new moons. In traditional South American agriculture, planting and harvesting occur during certain moon phases to increase yields. Since ancient times, humans have been surprised by the mysterious relationship between organisms and the moon. Recent studies have shown that human sleep, menstrual cycles, and bipolar disorder synchronize with new and full moons. That is, the activities of various organisms, including humans, are unconsciously influenced by the moon; however, the mechanism underlying this influence has not been clarified in any living organism. We succeeded in identifying pheromones that promote spawning at the time of the new and full moons by focusing on pufferfish that spawn in groups at the beach on the days of the new and full moons from mid-May to mid-July. Currently, we are attempting to understand the regulatory mechanisms underlying lunar rhythms.

　　　We possess a circadian clock within our bodies that maintains a 24-hour rhythm. The circadian clock regulates the rhythms of various physiological functions, including sleep-wake cycles, body temperature, blood pressure, and hormone secretion. In today’s around-the-clock society, living against circadian rhythms increases the risk of various diseases such as mental illnesses, lifestyle-related disorders, and cancer. Biologists and chemists have collaborated at the Institute for Transformative Biomolecular Research (ITbM) to develop biofunctional molecules that modulate the circadian clock. Cultured cells transfected with firefly luciferase gene, which exhibits a luminescent rhythm with a period of approximately 24 hours, were used to identify promising drug candidates from a vast array of compounds. We improved these candidate compounds through the integration of synthetic and computational chemistry and verified their effects at the individual level using zebrafish and mice. Additionally, we investigated the target molecules of these compounds to elucidate their action mechanisms. The compounds obtained in this study will contribute to basic studies to uncover new mechanisms of the circadian clock and be applied to treat clock-related diseases and increase animal reproduction.

　

In the tropics, temperatures remain stable throughout the year, whereas temperate zones experience significant seasonal temperature fluctuations. As a result, many organisms living in temperate regions possess excellent temperature-adaptation abilities characterized by flexibility and robustness. The medaka fish is one organism capable of adapting to a temperature range of 4°C to 40°C—an exceptionally wide range even among fish species. However, the mechanisms underlying the ability of medaka fish to adapt to such a broad range of temperatures remains unclear. Thus, we focused on the remarkable temperature adaptation ability of medaka fish and conducted analyses using omics analysis and genome-editing technologies. Through these studies, we aimed to elucidate the molecular mechanisms and acquisition principles of temperature adaptation abilities of this species. By applying the temperature adaptation mechanisms learned from medaka fish, we are advancing research toward achieving stable food production, even under climate change conditions. 

　We investigated the genes responsible for three small-bodied chicken breeds maintained in Japan and confirmed that the cause of dwarfism was an abnormality in the growth hormone receptor. Growth hormones are responsible for normal growth and are secreted mainly from the anterior pituitary gland. These hormones promote normal growth of individuals in birds, mammals, and fish. Short stature, acromegaly, and gigantism in humans are caused by decreased or increased growth hormone activity. In addition, growth hormone action has been found to be involved not only in bone growth but also in carbohydrate, lipid, and protein metabolism, fertility acquisition, and innate and adaptive immunity systems involved in biological defense. Chickens have long been closely related to humans as both pets and industrial animals, and their diversity varies with breeds and strains possessing unique traits (body size ranging from 7 to 0.6 kg, sexual maturity from 16 to 30 weeks old, and a variety of plumages, temperaments, and body shapes). We sought to elucidate and control their advantages and realize their potential hidden in chickens.