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1. The birth of the Laboratory of bioorganic chemistry in Department of Chemistry II, School of Science: The first 10 years (1966–1975)

Professor Koichi Yagi (1966–1989)
Associate Professor Koki Uchida (1966–1973)
Assistant Professor Fumi Morita (1966–1973)
Assistant Professor Yoichi Yazawa (1967–1975)

At the time, research on rabbit muscle myosin were initiated, using a variety of biochemical and physicochemical methods to elucidate the molecular mechanism of skeletal muscle contraction. At that time, Studies on enzyme kinetics were the mainstream topic of research; its integration with spectroscopic measurements led to our discovery that energy conversion in muscle is coupled to changes in the higher-order structure of myosin molecules. Moreover, efforts to overcome the low ionic strength insolubility of myosin when examining it from a physical chemistry point of view resulted in the establishment of a method of preparation of soluble myosin fragments. These fragments were generated by limited proteolysis using chymotrypsin, which retained their motor protein function. We synthesized a fluorescent adenosine triphosphate (ATP) derivative that could be used as a source of energy for muscle contraction, and we also succeeded in following the energy transduction process with high sensitivity by spectroscopy.

2. The next 10 years (1976–1985)

Professor Koichi Yagi (1966–1989)
Associate Professor Fumi Morita (1973–1989)
Assistant Professor Michio Yazawa (1975–1985)
Assistant Professor Mikiharu Yoshida (1976–1985)

Research on muscle contraction and energy transduction further developed into investigations on protein-protein interactions between myosin and actin, as well as conjugate molecular mechanisms of myosin ATPase reactions. The laboratory continued to use the rabbit as an animal model. On the other hand, scallop breeding became popular in Hokkaido and research into the molecular mechanisms of adductor muscle contraction progressed. The experience of the oil shock era fueled studies on low-energy muscle contraction in white smooth muscle (the adductor muscle) as a catch mechanism. Muscles contract when necessary. Although this seems obvious, in the world of chemistry, reactions seem one-sided until reaction substances and catalysts reach equilibrium. The cell contains both catalysts and reaction substrates, but reactions only occur when required. During this time, studies on the regulation of contraction were launched to elucidate its mechanism. During the process of examining myosin kinases and the meaning behind myosin phosphorylation, we found calmodulin. This discovery opened up a new avenue for the regulation of contraction via calcium ions (Ca2+) while simultaneously investigating the physiological function of calmodulin as a second messenger of intracellular signal transduction pathways. Studies of calmodulin using protein chemistry and physical chemistry began at this time, and research collaborations emerged within university, as well as with other local and international institutions.

3. From the Showa to Heisei period (1986–1995)

Professor Fumi Morita (1989–1996)
Associate Professor Michio Yazawa (1989–1994)
Assistant Professor Tsuyoshi Katoh (1990–2000)
Assistant Professor Masumi Eto (1991–1999)

After the retirement of Professor Yagi, Professor Fumi Morita spearheaded our laboratory’s studies. Research on skeletal muscle moved towards identifying interaction sites between myosin and actin. Furthermore, investigations on the mechanisms of contraction using vascular smooth muscle cells from pig arteries were initiated. On the other hand, research on calmodulin using baker’s yeast, as well as using colon Bacillus for protein production were launched. Numerous other organisms were also used in protein production, including rabbits, scallops, pigs, baker’s yeast, and Escherichia coli. To elucidate the mechanism of contraction regulation in the smooth muscle, we conducted experiments involving the phosphorylation and de-phosphorylation of myosin, and discovered the myosin phosphatase inhibitor protein (CPI-17) in aortic smooth muscle. By combining the chemical cross-linking and observation of myosin molecules using an electron microscope, we performed studies of the molecular mechanism of myosin phosphorylation in relation to the regulation of muscle contraction.

4. Reorganization of the department placing greater emphasis on graduate education and research activities, and the establishment of course of biomolecular chemistry in division of chemistry (1995–2006)

Professor Michio Yazawa (1995–2009)
Associate Professor Masayuki Takahashi (2001–present)
Assistant Professor Hajime J. Yuasa (2000–2002)
Assistant Professor Akiko Nakatomi (2003–present)

In April 1995, we identified ourselves as a member of the course of biomolecular chemistry in Division of Chemistry, Graduate School of Science, and received the title of Bioorganic Chemistry Laboratory. In March 1996, Professor Morita retired and the research continued as a 3-person team.

In addition to research on the physiological functions of calmodulin using baker’s yeast and scallop testes, we began elucidating the function of calcineurin and the newly discovered calcineurin-binding protein, CaNBP75. We approached the research of contraction regulation mechanisms using smooth muscles by looking into myosin kinases and phosphatases that comprise the phosphorylation regulatory system, as well as endogenous inhibitory protein (CPI-17). Furthermore, we took a multi-faceted approach in determining the molecular mechanism of cellular motility and changes in morphology, focusing on non-muscle cell myosin.

5. Reorganization of graduate schools and research institutes (2006–2009)

Professor Michio Yazawa (1995–2009)
Associate Professor Masayuki Takahashi (2001–present)
Assistant Professor Akiko Nakatomi (2003–)

Since April 2006, we continued our research as a member of the Department of Chemistry in Faculty of Science. We undertook the existing research and continued a two-pronged research program of investigating the mechanism of calcineurin and CaNBP75 in the testes, focusing on non-muscle cell myosin to elucidate the molecular mechanism of cell motility and changes in morphology.

6. Induction of Professor Murakami (2009–present)

Professor Yota Murakami (2009–present)
Associate Professor Masayuki Takahashi (2001–present)
Assistant Professor Akiko Nakatomi (2003–present)
Assistant Professor Shinya Takahata (2009–present)

Professor Yazawa’s retirement brought Professor Yota Murakami, who was then affiliated with Institute for Virus Research, Kyoto University, to our group. In addition to Takahashi and Nakatomi, Assistant Professor Takahata joined us, resulting in a 4-person team to begin a fresh start.

Professor Murakami’s past research on the composition of heterochromatin and mechanisms of regulation was integrated into our research focus. Using fission yeast as a model organism, we are currently investigating how heterochromatin, a higher-order chromatin structure, is involved in the regulation of gene expression, as well as in the function and maintenance of chromosomes. We are also conducting studies on the formation and maintenance of heterochromatin, as well as the regulation of various functions of heterochromatin by using techniques in molecular biology and biochemistry.

In addition, we are continuing our research on the molecular mechanisms of cell motility and changes in morphology in myosin II, as well as on the function of calcineurin and CaNBP75 in the testes. The results generated in each of these research topics feeds the other themes, thus sustaining our curiosity and excitement to continue our research.