Research

Introduction

Research in the Withers Group primarily focuses upon enzymes involved in glycoside cleavage and synthesis, with special emphasis upon their mechanisms. Research also focuses upon exploitation of the understandings developed. Applications range from development of new enzyme-based synthetic methodologies to new therapeutics and imaging agents. Of particular importance to this research area has been the classification of glycosidases and other carbohydrate – processing enzymes into sequence-based families by Bernard Henrissat (Marseilles). The CAZy website and the associated Wiki site CAZypedia are constant reference points and sources of inspiration.

Techniques commonly employed include:

•  Synthesis of sugar-based substrates and inhibitors, particularly fluorinated sugars.
•  Enzyme kinetic analysis, both steady state and pre-steady state
•  Molecular Biology – cloning and expression, site-directed mutagenesis and directed evolution
•  Applications of NMR to enzymology – in collaboration with Dr. Lawrence McIntosh
•  Applications of mass spectrometry to enzymology using our jointly owned Q-TOF, MALDI-TOF, FT-ICR and ORBITRAP instruments
•  Applications of X-ray crystallography – in collaboration with a number of crystallographers, most notably Dr. Natalie StrynadkaDr. Gary Brayer and Dr. Gideon Davies
•  High-throughput screening

Collaborators:

Austria Institute of Organic Chemistry: Arnold Stuetz and Tanja Wrodnigg

The Hospital for Sick Children / University of Toronto: Don MahuranMike Tropak

Ryerson University – Toronto: Warren Wakarchuk

Simon Fraser University: Masa Niikura

University of Alberta: Michael James

University of British Columbia: Ray AndersenGary BrayerLorne ClarkeCarl Hansen, Jay KizhakkedathuSteve HallamLawrence McIntoshJohn McNeill, Natalie Strynadka, Joerg Bohlmann

University of Waterloo: David Rose

University of York: Gideon Davies