Research in my group centers around applications of solid-state Nuclear Magnetic Resonance (NMR) to various problems in structural biology and biophysics. We are particularly interested in structure determination and dynamic characterization of membrane-embedded proteins. This is a very wide class of proteins – approximately a third of all proteins are predicted to associate with lipid membranes – yet only a handful (about 200) of them have been structurally characterized at atomic resolution. Most of our research efforts focus on the development of new and efficient ways to determine structures of these proteins. Knowledge of these structures not only contributes to the fundamental understanding of membrane biology, but has long-standing practical implications because about 50% of all membrane proteins are potential drug targets.
Although solid-state NMR is the main theme in our research, we also use other complimentary approaches such as solution NMR, computational and biophysical methods, and chemical and molecular biology approaches to synthesis and purification of peptides and proteins. We have extensive collaborations with other research groups at Guelph, in particular with the Leonid Brown’s lab (physics) and George Harauz (MCB). Among proteins we currently study are light-driven bacterial proton pump proteorhodopsin, photosensory cyanobacterial rhodopsin (collaborations with Drs. L. Brown, K. Jung (Sogang University, South Korea), and with Dr. T. Herrmann, (CNRS, ENS Lyon, France)), and myelin basic protein (collaboration with Dr. Harauz).
Proteorhodopsin is a heptahelical integral membrane protein that functions as a proton pump. We are interested in determining its three-dimensional structure in the native membrane environment. We have already made significant progress towards this end, which allows us to look beyond structure, and start elucidating such important questions as protein-lipid interactions, protein dynamics and protein folding in the lipid membrane. Solid-state NMR is well suited to contribute precise site-specific information on both structural detail and the dynamic time scale of these fundamental processes, something that cannot be readily achieved by other methods.
Sensory rhodopsin of Cyanobacteria. We recently initiated studies of novel photosensory rhodopsin, which is likely involved in a photo-transduction cascade ultimately resulting in gene regulation.
Myelin Basic Protein. In collaboration with the group of Prof. G. Harauz, we are investigating the structural conformation of myelin basic protein (MBP) in its association with lipids. This protein is involved in maintaining the structure of the lipid-rich myelin sheath in the central nervous system. MBP is chemically altered (deiminated) in the neurodegenerative disease multiple sclerosis (MS), resulting in sheath degradation and autoimmune attack. We use solid-state NMR to gain insight into the nature of MBP-lipid interactions at atomic level resolution. Fundamental questions are how this protein associates with lipids and how this association is affected by deimination. Our research will help shed light on the molecular basis of MS.
Development of NMR Techniques. Applications of solid-state NMR to protein structure determination require constant development of new methodologies. This drives our interest in fundamental and applied aspects of NMR spectroscopy: the development of new approaches for sensitivity enhancement of solid-state NMR experiments, new methods for spectral assignments, and measurements of structural constraints. Of particular interest is the development of methods for detailed understanding of molecular motions in proteins.