I am interested in the details of how evolution can harness natural variations in proteins to generate improved or new functions. My current work focusses on discerning the molecular mechanism in the evolution of antibiotic resistance proteins. To do this, I employ a technique called “deep mutational scanning”, which allows me to assess the functional potential of all single amino acid mutants of the metallo-β-lactamase family of antibiotic degrading enzymes. Combining this phenotypic data with additional data from biochemical, biophysical and bioinformatics analysis, I hope to paint a large scale picture that describes the evolutionary mechanism of metallo-β-lactamases.

Publications

• Miton, C. M., Chen, J. Z., Ost, K., Anderson, D. W. & Tokuriki, N. Chapter Eleven – Statistical analysis of mutational epistasis to reveal intramolecular interaction networks in proteins. in Methods in Enzymology (ed. Tawfik, D. S.) vol. 643 243–280 (Academic Press, 2020).
• Chen, J. Z., Fowler, D. M. & Tokuriki, N. Comprehensive exploration of the translocation, stability and substrate recognition requirements in VIM-2 lactamase. eLife 9, e56707 (2020).
• Socha, R. D., Chen, J. & Tokuriki, N. The Molecular Mechanisms Underlying Hidden Phenotypic Variation among Metallo-β-Lactamases. Journal of Molecular Biology 431, 1172–1185 (2019).
• Baier, F., Chen, J., Solomonson, M., Strynadka, N. C. J. & Tokuriki, N. Distinct Metal Isoforms Underlie Promiscuous Activity Profiles of Metalloenzymes. ACS Chemical Biology 10, 1684–1693 (2015).