About our research interests
My research group is interested in membrane structural and functional molecular biology and biophysics, macromolecular X-ray crystallography, single-particle cryo-electron microscopy, membrane lipids and proteins, membrane mimetics, robotics, structure-function relationships, and structure-based antibiotic, vaccine and antiviral drug design and development.
A healthy cell, and by extension a healthy organism, requires intact, selectively permeable membranes. Whist lipids are essential to membrane form and function, membrane proteins can be viewed as vital, nanometer-sized molecular robots that serve critical signal transducing, enzymatic, transport and structural roles. As targets of disease causative and treatment agents, the health consequences of membrane protein malfunction are obvious. Our approach to understanding how these proteinaceous nano-machines perform at a molecular level relies on obtaining a high-resolution structure for each primarily using macromolecular X-ray crystallography and more recently by single-particle cryo-electron microscopy. In the Membrane Structural and Functional Biology Group, a multifaceted approach is taken to produce structure-grade crystals for crystallographic purposes. Emphasis is placed on crystallization in lipid mesophases by what is referred to as the in meso method. This is proving to be a generally useful approach for membrane protein structure determination. Because crystallization takes place in a membrane environment, the in meso method is likely to be favoured by the target protein. We have built state-of-the-art robots that perform in meso crystallization in high-throughput fashion and that require miniscule amounts of protein and lipid. They are used to generate 3-dimensional crystals for high-resolution structure determination of a select group of membrane proteins and their complexes. The target group covers a broad range of membrane protein types including eukaryote and prokaryote, integral and peripheral, monomeric and multimeric proteins, as well as protein-protein, protein-peptide and protein-ligand complexes. The bulk of these target proteins are produced in-house; others are provided by collaborators.
In parallel with on-going crystal structure determination projects, considerable effort is devoted to improving crystallogenesis and to broadening the range of membrane protein targets that yield to structure determination. This is done by implementing a synthesis program whereby lipids with desirable physico-chemical characteristics are produced for use in in meso crystallization trials. The molecular mechanism of crystal nucleation and growth is also being studied with a view to more rational and productive crystallogenesis. Success in obtaining crystals, and ultimately the atomic structure of membrane proteins will enhance our understanding of and control over some of the most fundamental processes underlying cellular function that are integral to human health.
Latest undertakings in the group involve applying the glimpses into membrane protein function we gain from structure to the design and development of antibiotics, vaccines and antiviral drugs. Some of the vaccine and antiviral drug work addresses the recent Covid-19 pandemic and its causative agent, the SARS-CoV-2 virus.
Find some more useful information on the science.sciencemag.org website.