Biophysicist in Profile

“Don’t addict yourself to self-judgment,” advises Shin’ichi Ishiwata, Professor of Physics at Waseda University in Japan, Director of Waseda Bioscience Research Institute in Singapore (WABIOS), and Editorial Board member for the Biophysical Journal. He knows well that self-doubt can be a researcher’s greatest nemesis.

Fellow Waseda professor Kazuhiko Kinosita, Jr., considers Ishiwata “the most productive biophysicist in Japan, who  produced many active researchers, including famous professors.” Yet as a young student who failed some critical exams, including the one for college entrance, Ishiwata was not at all sure that he could become the kind of scientist he admired and wanted to be.

After completing undergraduate work in physics at the University of Tokyo, he went to Nagoya University for his masters and PhD degrees. He later did postdocs at Boston Biomedical Research Institute and Massachusetts Institute of Technology.

Ishiwata’s confidence grew as a graduate student in Fumio Oosawa’s lab. Mentors Oosawa and Satoru Fujime conveyed that “a scientist’s research is not fulflled by quick understanding of the established science only, but by putting forth all the energy, talent, and character we possess.” As Oosawa always showed interest in Ishiwata’s data and ideas, even when the approaches were premature, and Fujime, although “severe for science but very gentle in life,” gave positive suggestions, Ishiwata began to enjoy research.

Ishiwata regrets that as a graduate student he did not choose subjects of greater scientifi c importance, but acknowledges that it is diffi cult-to impossible to decide beforehand the scientific significance of a given subject. Relying on his own interests, ideas, and approaches in research, he gained self-assurance in the process of solving problems as he encountered them.

In 1975, Ishiwata’s confi dence took another blow. His most important paper—the core of his doctoral thesis—was not accepted into any publication. His thesis dealt with utilizing dynamic (quasi-elastic) light scattering to study the effect of regulatory proteins (Ca2+ ions) and myosin binding on the flexural rigidity of actin fi laments in solution. Th e paper proposed that myosin binds with either one or both, depending on the solvent conditions. About 20 years
later, single-molecule unbinding-force measurements confi rmed his thesis (c.f. Nature 1995).

Ishiwata sees that painful rejection of his paper as important in helping determine the subject of his future research. Since spectroscopic techniques yielded only averaged characteristics of an ensemble of proteins, he constructed his own research method. He focused on his long-held interest in striated muscle— “how a beautiful structure is self-organized, and how it is related to force-generating function.”

This tackled to reconstitution of the structure and function of the thin (actin) filaments in striated muscle, especially cardiac muscle, then to defining the mechanism of Spontaneous Oscillatory Contraction (SPOC) of striated muscle that occurs at intermediate activation conditions between full activation and relaxation. It was an important breakthrough regarding a phenomenon that had been “almost completely ignored,” he says.

Identifying SPOC illustrates Ishiwata’s favorite way of research, serendipity, or “finding new phenomena and mechanisms through observations and experiments by my own sense of science. The finding was only a happening, but it took two months to fi nd the solvent conditions in which the steady SPOC is always observed.”

Ishiwata’s current research interests go beyond the mechanical and physiological import of SPOC to bio-motile systems focusing on the structural and functional hierarchy from single molecules (myosin, kinesin, actin) to macromolecular assemblies (myofi brils, meiotic spindle) and cells (cardiac, HeLa, etc.). He expects that the multiplex network of Chemo-Mechanical Feedback (CMF) loops exist over various hierarchical levels. He proposes that the heart is a typical organ in which nano and macro, i.e., mechano-chemical functions of molecular motors and heartbeat, are directly coupled to each other through the CMF loops.

Serendipity touched Ishiwata’s life even before his July 1945 birth, three weeks before World War II ended. His pregnant mother fled her central Tokyo home for her birthplace in the country a few days before the largest of the air raids turned the center of the city into a burnt fi eld. “If her escape had been a little later,” Ishiwata says, “I would not have been born.”

“Shin’ichi is a true philosopher,” says Dave Thomas, William F. Dietrich Professor of Structural Biology at the University of Minnesota and Ishiwata’s collaborator and friend. “On his science, culture, or family, he expresses himself eloquently and passionately. He appreciates aesthetic aspects of his work, the complex beauty of dynamic motor protein assemblies. He follows his dreams and encourages others to follow theirs.”

Kinosita says that Ishiwata “seduced” him into biophysics. “Shin’ichi can never throw away anything—particularly people.” In working together on a project as students, they found that their preferred roles complemented each other—roles they have maintained for forty years.

Ikuko Fujiwara, a postdoc fellow with the National Institutes of Health in Bethesda, Maryland, studied with Ishiwata at Waseda. “He once said the fun part of doing science is considering unique approaches. He greatly influenced my ability to analyze data and handle issues at hand. Any inefficiency in his method is cancelled by his helping students maintain their motivation and enthusiasm.”

“As students experience and understand that good results were obtained by their own ideas and abilities, no matter how tiny the problem is, they gain confi dence in their future career,” says Ishiwata.

Ishiwata challenges a new research theme by working with the Human Frontier Science Program (HFSP), which “supports novel, innovative, and interdisciplinary basic research focused on the complex mechanisms of living organisms.”

Ishiwata’s wife, Akiko, “works hard for our family as a homemaker” and sings with a chorus that performs for people in nursing homes. Th eir son, Shintaro, a material scientist for RIKEN, is married and has a son. His daughter, Satoko, born during their years in Boston, married recently. A second son, Shusuke, is an engineer and works for Canon.

Ishiwata relieves stress with music, listening to Japanese pop songs of the sixties and seventies or American singers like Connie Francis, Doris Day, or Andy Williams. “When the mood strikes me, I unconsciously hum, especially while working in the laboratory.”

Above right: Ishiwata family with Dave and Jenny Thomas at Ishiwata’s home in Tokyo.
From left to right, front: Akiko (Ishiwata’s wife) Jenny and Dave Th omas; rear: Shusuke, Mamiko (Shintaro’s wife), Shintaro, and Shin’ichi Ishiwata.

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