Tokuriki, Nobuhiko - University of British Columbia - Department of Biochemistry and Molecular Biology

个人简介

Osaka University, Osaka, Japan, 2004, PhD Weizmann Institute of Science, Rehovot, Israel, 2004, Postdoctoral Fellow University of Cambridge, UK,, 2009, Postdoctoral Fellow

研究领域

Experimental evolution of proteins and molecular networks. Evolution provides the theoretical framework by which we can understand biology. Understanding evolutionary processes is also crucial for engineering new proteins, metabolic pathways and organisms. My group uses ‘experimental evolution’ to reconstruct evolutionary trajectories of biological molecules in the laboratory, and to perform deep characterization of evolutionary trajectories and intermediates to examine various aspect of evolutionary dynamics. In experimental evolution, all parameters such as mutation rate and type, selection pressure and the environment are tunable, thus we can controllably test various aspects of molecular evolution. The evolutionary intermediates obtained in the experiments represent a molecular “fossil record”, and enable us to explore step-by-step evolution of molecular function. Moreover, functional and structural characterization of the intermediates significantly contributes to the long-standing question in protein science of “how function and structure are related” . The research process specifically involves i) recreating evolutionary processes to acquire a new protein function or a new and protein network in the laboratory using synthetic biology and experimental evolution. This typically involves iterative cycles of gene diversification and gene library screening/selection. ii) Characterizing the effects of mutations obtained in evolution to identify how epistasis (interaction between mutations) restricts evolutionary trajectories, and reveal mechanisms underlying the epistasis. In particular, how and why the order of mutations accumulated in the evolution is crucial to accomplish functional and structural transition. iii) Characterizing intermediates in the evolution with various biochemical and biophysical techniques to investigate the relationship between sequence, function and structure, and in particular the interplay between multiple functionality and conformational diversity. iv) Applying our knowledge of molecular evolution to create de novo proteins and metabolic pathways for industrial and medical uses.

近期论文

查看导师新发文章（温馨提示：请注意重名现象，建议点开原文通过作者单位确认）

Wyganowski KT, Kaltenbach M, Tokuriki N.”GroEL/ES buffering and compensatory mutations promote protein evolution by stabilizing folding intermediates” J Mol Biol, 425, 3403-14, 2013 Socha RD, Tokuriki N. “Modulating protein stability – directed evolution strategies for improved protein function”. FEBS J, 280, 5582-95, 2013 Tokuriki, N., Jackson, C.J., Afriat-Jurnou, L., Wygnowski, K.T., Tang, R., Tawfik, D.S., “Diminishing returns and tradeoffs constrain the laboratory optimization of an enzyme” Nature Communications, 3:1257 | DOI: 10.1038/ncomms2246, 2012 Babtie, A., Tokuriki, N. & Hollfelder, F. “What makes an enzyme promiscuous?” Curr Opin Chem Biol, 2, 200-207, 2010 Tokuriki, N. & Tawfik, D. S. “Stability effect of mutations and protein evolvability” Curr Opin Struct Biol, 5, 596-604, 2009 Tokuriki, N. & Tawfik, D. S. “Chaperonin overexpression promote genetic variation and enzyme evolution” Nature, 459, 668-673, 2009 Tokuriki, N. & Tawfik, D. S. “Protein dynamism and evolvability” Science, 324, 203-207, 2009 Tokuriki, N., Stricher, F., Serrano, L., & Tawfik D. S. “How protein stability and new functions tradeoff” PLoS Computational Biol, 4 (2) e1000002, 2008 Tokuriki, N., Stricher, F., Schymkowitz, J., Serrano L., & Tawfik, D. S. “The Stability Effects of Protein Mutations Appear to be Universally Distributed” J Mol Biol, 369, 1318-1322, 2007