Dr. Wayne Patrick
Lecturer in Biochemistry

Background

Post-doctoral fellow, Emory University, 2003-07
Ph.D., University of Cambridge, 2003
B.Sc. (Hons), University of Otago, 1999

Research Interests

Where do new enzymes and pathways come from?

All organisms maintain the ability to evolve in response to changing environments. The research in my lab focuses on the molecular processes that underlie adaptive evolution, and in particular:

• What latent functions lurk within proteomes?
• Are these secondary activities readily evolvable?

The first question was addressed by using the tools of functional genomics to survey the entire proteome of a model bacterium, Escherichia coli, for proteins with the ability to multi-task. Contrary to the traditional "one enzyme, one substrate" view of enzyme specificity, our results suggest that many proteins (and perhaps all) possess secondary activities that become physiologically relevant, given an appropriate evolutionary pressure. One avenue of future work will centre on the enzymatic and evolutionary functions of cryptic genes (i.e. those not normally expressed in the cell). Our studies have also emphasized the role of regulating gene expression as an evolutionary strategy. A second project will investigate this, with respect to the evolution of antibiotic resistance.

The techniques of directed evolution allow us to mimic protein evolution in the lab. Preliminary results with enzymes in purine and tryptophan metabolism confirm a model in which secondary activities are indeed evolvable. Moreover, a single enzyme from purine biosynthesis, PurF, appears to be a multi-tasking champion, able to catalyse at least three different reactions. However, many of the biochemical details of this system remain to be elucidated.

More information is available on my lab website.

Students interested in these fields, including molecular evolution, protein engineering and enzymology, should feel free to contact me to discuss possible Ph.D. or M.Sc. projects.

Selected Publications

• Patrick, W.M. and Matsumura, I. (2008). A study in molecular contingency: glutamine phosphoribosylpyrophosphate amidotransferase is a promiscuous and evolvable phosphoribosylanthranilate isomerase. Journal of Molecular Biology, 377, 323-336.


• Patrick, W.M., Quandt, E.M., Swartzlander, D.B. and Matsumura, I. (2007). Multicopy suppression underpins metabolic evolvability. Molecular Biology and Evolution, 24, 2716-2722.


• Firth, A.E. and Patrick, W.M. (2005). Statistics of protein library construction. Bioinformatics, 21, 3314-3315.


• Patrick, W.M. and Blackburn, J.M. (2005). In vitro selection and characterization of a stable subdomain of phosphoribosylanthranilate isomerase. FEBS Journal, 272, 3684-3697.


• Patrick, W.M. and Firth, A.E. (2005). Strategies and computational tools for improving randomized protein libraries. Biomolecular Engineering, 22, 105-112.


• Lutz, S. and Patrick, W.M. (2004). Novel methods for directed evolution of enzymes: quality, not quantity. Current Opinion in Biotechnology, 15, 291-297.


• Patrick, W.M., Weisner, J. and Blackburn, J.M. (2002). Site-directed mutagenesis of Tyr354 of Geobacillus stearothermophilus alanine racemase identifies a role in controlling substrate specificity and a possible role in the evolution of antibiotic resistance. ChemBioChem, 3, 789-792.

For a complete list of publications, click here.