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Structural Biology Nishimasu Laboratory

Structural Biology
Nishimasu Laboratory

Understanding of the Structure and Function of Diverse Proteins and Nucleic Acids, and Development of New Technologies

Structural and functional elucidation of proteins and nucleic acids

Proteins and nucleic acids (DNA and RNA) are involved in a wide variety of biological processes. While ordinary proteins act like “lock and key” on specific substrates, some proteins associate with RNAs, which determine the specificity for its target nucleic acids. For example, the Cas9 protein from the prokaryotic CRISPR-Cas adaptive immune system associates with a guide RNA and cleaves a doublestranded DNA that is complementary to the RNA guide. Thus, Cas9 has been applied to various new technologies, including genome editing. We have determined the structures of protein-nucleic acid complexes, such as Cas9, Cas12 and Cas7-11, and have elucidated their action mechanisms. In addition, we performed structurebased molecular engineering to develop new genome-editing technologies. Using multiple techniques, such as biochemistry, X-ray crystallography, cryo-electron microscopy, and single-molecule observation, we elucidate the action mechanisms of diverse proteins and nucleic acids, understand biological processes at atomic levels, and develop new useful technologies. Furthermore, we aim to explore novel enzymes that have not yet been discovered, and to elucidate their structure and function.

Crystal structure of CRISPR-Cas9
Cryo-EM structure of CRISPR-Cas7-11

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I have always loved professional wrestling and martial arts, and during my university years, I was a member of the Shorinji Kempo club. As a graduate student, I attended a kickboxing gym. Moreover, after becoming a researcher, I started boxing since there was a boxing gym nearby. Since I have a personality that likes to pursue things thoroughly, I decided to get a professional license in 2012. Boxing also serves as a stress reliever, and the physical and mental strength I gained from it has been beneficial to my research. In the past ten years, there have been unexpected technological advancements that have made previously impossible research possible. The speed of technological innovation is accelerating year by year, making it difficult to predict research outcomes ten years from now. Through my research so far, I have come to understand that my strengths lie in techniques for closely examining and altering the molecular structures of proteins and nucleic acids. Moving forward, I plan to continue my research, leveraging these strengths while flexibly incorporating new technologies and following my interests.