Graduate School of Frontier Sciences, The University of Tokyo Department of
Integrated Biosciences

I spent both my undergraduate and graduate years at the Faculty of Pharmaceutical Sciences and the Graduate School of Pharmaceutical Sciences at the University of Tokyo. In my fourth undergraduate year, I joined to a laboratory that studied protein structures using X-ray crystallography, without any clear sense of purpose and without fully understanding what kind of research the lab was conducting. Since then, I have continued in this field for nearly 25 years. I believe it was a kind of serendipitous encounter. Perhaps the straightforward methodology of structural biology—understanding how proteins function by examining their three-dimensional structures—resonated with me. At the time, X-ray crystallography was the primary method for determining protein structures. However, this technique requires the painstaking and highly patient task of producing protein crystals. Small tricks in crystallization or subtle differences in how the crystals are handled can make the difference between success and failure in structure determination. I think I was also drawn to this craftsman-like quality of the method, with its air of meticulous and artisanal skill.

Structural biology has changed dramatically over the past 25 years. Around a decade ago, a series of technological breakthroughs made it possible to determine structures at near-atomic resolution using cryo-electron microscopy (cryo-EM), and the field has rapidly advanced since then. Today, researchers routinely choose between X-ray crystallography and cryo-EM depending on the sample characteristics and the nature of the project. A few years ago, the release of AlphaFold2, a program capable of accurately predicting protein structures, enabled researchers outside the field of structural biology to begin incorporating structural insights into their work. Moreover, it is now becoming possible to design proteins with desired functions entirely in silico. Thanks to advances in cryo-EM, the time required for structure determination has been drastically reduced—so much so that it's no longer unusual to determine a structure on the same day a purified sample becomes available.

Despite these rapid and remarkable changes in the field, one thing remains the same: the experience of facing a colorless, transparent (though sometimes not) protein sample in a test tube. The excitement of imagining what that protein might look like, of hoping to "see" it, and of running the experiment with anticipation—that thrill, and the moment when a structure is finally obtained and something previously unknown becomes clear—feels much the same as it did 25 years ago. While cherishing the joy of research, I hope to continue pursuing the invisible, driven by the same curiosity and wonder that first brought me into this field.