Faculty

• BSc (University of British Columbia)
• PhD (University of British Columbia)

• Molecular Evolution
• Catalysis
• Physical Organic Chemistry

The main theme of my research is the use of molecular evolution experiments (in vitro selection) to discover new catalysts for synthetically or bio-medically relevant chemical reactions. The discovery of catalysts made out of DNA (“DNAzymes”) is generally a much simpler process than the discovery of catalysts made out of protein (“enzymes”). Unfortunately, DNA is not equipped with the diverse array ofcatalytically useful chemical functionalities present in proteins. As a result, DNAzymes are typically far inferior catalysts compared to their protein counterparts. We will try to improve the catalytic ability of DNAzymes by introducing “protein-like” synthetic modificationsin various ways. RNA cleavage and glycosyl-transfer reactions will be the initial targets for catalyst discovery. Once catalysts have been identified, the real fun begins (from my point of view) –characterizing their active site mechanisms. These projects involve techniques in molecular biology and synthetic organic, bioconjugate, and physical organic chemistry. Most importantly, I hope students will gain a deeper understanding of the fundamentals of catalysis and enzymology.

Opportunities also exist to work on a collaborative project with researchers at SFU (Profs. Dipankar Sen and Hogan Yu). The goal of this project is to create electronic sensors made out of DNA for the detection of clinically relevant analytes. Double-stranded DNA has an intrinsic ability to conduct electric charges, much like a “molecular-scale wire”. Electrical switches that respond to the presence of an analyte can be engineered by inserting a small DNA structure into the double-helix that binds to the analyte. Changes in DNA structure that accompany analyte binding serve to modulate the rate of charge transfer through the DNA. Sensor devices, with a simple electrical readout, can then be created by attaching the electrical switch DNAs to an electrode surface.This project will involve molecular evolution, and DNA photo-and electro-chemistry.

Selected Publications

• Thomas, J.M., Yu, H.-Z., Sen, D. (2012) A Mechano-electronic DNA Switch. J. Am. Chem. Soc.134: 13738-13748.
• Thomas, J.M., Chakraborty, B., Sen, D., Yu, H.-Z. (2012) Analyte-Driven Switching of DNA Charge Transport: De Novo Creation of Electronic Sensors for an Early Lung Cancer Biomarker. J. Am. Chem. Soc.134:13823-13833.
• Thomas, J.M., Yoon, J.-K., Perrin, D.M. (2009) Investigation of the Catalytic Mechanism of a Synthetic DNAzyme with Protein-like Functionality: An RNaseA Mimic? J. Am. Chem. Soc.131: 5648-5658.
• Thomas, J.M., Perrin, D.M. (2009) Probing General Acid Catalysis in the Hammerhead Ribozyme. J. Am. Chem. Soc.131: 1135-1143.
• Thomas, J.M., Perrin, D.M. (2008) Probing General Base Catalysis in the Hammerhead Ribozyme. J. Am. Chem. Soc.130: 15467-15475.
• Thomas, J.M., Perrin, D.M. (2006) Active Site Labeling of G8 in the Hairpin Ribozyme: Mechanistic Implications for General Base Catalysis. J. Am. Chem. Soc.128: 16540-16545.
• Thomas, J.M., Ting, R., Perrin, D.M. (2004) High Affinity DNAzyme-based Ligands for Transition Metal Cations: A Prototype Sensor for Hg²⁺. Org. Biomol. Chem. 2:307-312.
• May, J.P., Ting, R., Lermer, L., Thomas, J.M., Roupioz, Y., Perrin, D.M. (2004) Covalent Schiff Base Catalysis and Turnover by a DNAzyme: A M²⁺-Independent AP-Endonuclease Mimic. J. Am. Chem. Soc.126: 4145-4156.
• Thomas, J.M., Walker, N.R., Cooke, S.A., Gerry, M.C.L. (2004) Microwave Spectra and Structures of KrAuF, KrAgF, and KrAgBr; ⁸³Kr Nuclear Quadrupole Coupling and the Nature of Noble Gas-Noble Metal Halide Bonding. J. Am. Chem. Soc.126: 1235-1246.