Osamu Nureki


Professor Nureki is a structural biologist who has published numerous articles on prestigious scientific journals in the CRISPR field (e.g. Cell, 2014, 2015 & 2016). Dr. Nureki has a long-lasting collaboration relationship with Dr. Feng Zhang at Broad Institute, one of the key discoverers of CRISPR technology. Dr. Nureki and Dr. Zhang co-publish many scientific papers and co-file key critical patents on CRISPR and gene editing technologies. Dr. Nureki receives his PhD from University of Tokyo. He is currently a Professor at Department of Biological Sciences, Graduate School of Science in the University of Tokyo. 

He was awarded the JSPS PRIZE in 2008, the Mochida Memorial Research Prize in 2009 and the Inoue Prize in 2011 for his research into “the genetic code translation and the definition of protein synthesis mechanism”, and was awarded the Uehara Prize and Takeda Medical Prize in 2014 for his research into “molecular mechanism of membrane transport.”

 

Molecular mechanism of CRISPR and structure-based development of genome editing tool towards medical applications


The CRISPR-associated endonuclease Cas9 can be targeted to specific genomic loci by single guide RNAs (sgRNAs). We solved the crystal structure of Cas9, from 4 sources (984 a.a. to 1,629 a.a.), complexed with sgRNA and its target DNA at atomic resolutions. These high-resolution structures combined with functional analyses revealed the generality and diversity of molecular mechanism of RNA-guided DNA targeting by Cas9, and uncovered the distinct mechanisms of PAM recognition. On the basis of the structures, we succeeded in changing the specificity of PAM recognition, which paves the way for rational design of new, versatile genome-editing technologies. Recently, our high-speed atomic force microscopy (HS-AFM) analysis of SpCas9 visualized real-space and real-time dynamics of Cas9. We further solved the crystal structure of type-V CRISPR, Cpf1 in complex with crRNA and target dsDNA. The structure explains striking similarity and major differences between Cas9 and Cpf1.

 

1. “Crystal Structure of Cas9 in Complex with Guide RNA and Target DNA” H. Nishimasu, F. A. Ran, P. D. Hsu, S. Konermann, S. I. Shehata, N. Dohmae, R. Ishitani, F. Zhang F and O. Nureki. Cell 156, 935-949 (2014). doi: 10.1016/j.cell.2014.02.001.

2. “Crystal structure of Staphylococcus aureus Cas9” H. Nishimasu, L. Cong, W. X. Yan, F. A. Ran, B. Zetsche, Y. Li, A. Kurabayashi, R. Ishitani, F. Zhang and O. Nureki. Cell 162, 1113-1126 (2015). doi: 10.1016/j.cell.2015.08.007.

3.  “Structure and Engineering of Francisella novicida Cas9” H. Hirano, J. S. Gootenberg, T. Horii, O. O. Abudayyeh, M. Kimura, P. D. Hsu, T. Nakane, R. Ishitani, I. Hatada, F. Zhang, H. Nishimasu and O. Nureki. Cell 164, 950-961 (2016) doi: 10.1016/j.cell.

4.  “Structural basis for the altered Pam specificities of engineered CRISPR-Cas9” S. Hirano, H. Nishimasu, R. Ishitani and O. Nureki. Mol. Cell 61, 886-894 (2016) doi 10.1016/j.molcel.2016.02.018.

5.  “Crystal structure of Cpf1 in complex with guide RNA and target DNA” T. Yamano, H. Nishimasu, B. Zetsche, H. Hirano, I. M. Slaymaker, Y Li, I. Fedorova, T. Nakane, K. S. Makarova, E. V. Koonin, R. Ishitani, F. Zhang and O. Nureki. Cell 165, 949-962 (2016) doi: 10.1016/j.cell.2016.04.003.

6.  “Crystal Structure of the Minimal Cas9 from Campylobacter jejuni Reveals the Molecular Diversity in the CRISPR-Cas9 Systems” M. Yamada, Y. Watanabe, J. S. Gootenberg, H. Hirano, F. A. Ran, T. Nakane, R. Ishitani, F. Zhang, H. Nishimasu and O. Nureki. Mol. Cell. 65, 1109-1121 (2017).

7. “Real-space and real-time dynamics of CRISPR-Cas9 visualized by high-speed atomic force microscopy” M. Shibata, H. Nishimasu, N. Kodera, S. Hirano, T. Ando, T. Uchihashi and O. Nureki Nat. Commun. 8, 1430 (2017).