- Michael Smith Laboratories
- Department of Biochemistry and Molecular Biology
- Genome Sciences and Technology (GSAT) Graduate Program
- Postdoctoral Fellow, University of Cambridge, Cambridge, UK (2009-2011)
- Postdoctoral Fellow, Weizmann Institute of Science, Rehovot, Israel (2004-2009)
- Ph.D Osaka University, Osaka, Japan (2004)
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
- 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.
- 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.
- 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.
- Applying our knowledge of molecular evolution to create de novo proteins and metabolic pathways for industrial and medical uses.
Biochemistry, biotechnology, bioinformatics, biophysics, biomolecular engineering, enzymology, evolution, synthetic biology, protein chemistry, protein design
To learn more about the Tokuriki Lab, please visit tokurikilab.msl.ubc.ca.