Research Projects: By applying and developing magnetic resonance spectroscopic, molecular dynamics (MD) computer simulation, and other physical techniques (e.g. cryo-TEM), my research program is designed to investigate the relationship among structure, dynamics, electrostatic interactions and function of macromolecules and/or macromolecular assemblies. Macromolecules include proteins and peptides whereas macromolecular assemblies refer to liquid crystals including biological membranes. My research program involves a number of projects: Antimicrobial peptides (AMPs) MD simulations of liquid crystals Structural characterization of bio-molecules NMR methodology development Quantitative NMR HRMAS characterization of whole cell algae Drug/protein binding pocket characterization Interested Postdoctoral Fellows for NMR spectroscopic structure/function characterization of membrane-associated proteins should apply for a Killam, Cancer Research, NSERC or CIHR Fellowship. Interested graduate or undergraduate students should apply for NSERC, Cancer Research, or CIHR. .
AMPs: A wide variety of AMPs have been isolated from many plants and animals. AMPs in general are very effective at killing bacteria, enveloped viruses, parasites, and tumour cells. Furthermore, bacteria have difficulty developing resistance towards AMPs. Thus, AMPs are being considered as potential alternatives to current antibacterial agents particularly with the emerging problem of drug-resistant pathogenic bacteria. AMPs destabilize bacterial membranes. Slight amino acid mutations can cause significant alterations in activity, and general theories for AMP activity range from membrane carpeting to pore formation models that allow essential ions and metabolites to leak out.	The AMP associates with DPC (A) and DPC/SDS (B) micelles. However, it only forms an alpha helix when associated with DPC/SDS micelles that are a mimic for bacterial membranes. [Biochemistry, (2005) 44, 7282-7293].
Activities of AMPs are roughly correlated with the amphipathic and cationic nature of the peptides. However, there is no clear connection between the structure and mechanism of AMP activity. We have begun to determine structure, dynamics and multimerization propensity of AMPs in solution and in the presence of the lipid-like environments, in order to understand their mode of action.
MD Computer Simulations: Computer simulations are an excellent method for bridging the gaps between experiment and theory. We are conducting a comparative study to investigate peptide/membrane/water interactions of model membranes, and peptides that cause membrane destabilization, e.g. AMPs, and the active peptides of cell-to-cell FAST proteins. Although AMPs cause cell lysis, and fusion proteins cause membrane fusion, the initial stages of their mechanisms may be similar i.e. the proteins/peptides must initially destabilize the membrane which involves restructuring of the lipids and water molecules at the lipid surface. Regardless, the research will advance the knowledge and understanding of the mode of action of AMPs, fusion proteins and provide direction for future studies that will extend to antifreeze peptides, MA receptor proteins, antibiotics, and ion channel peptides.	From MD simulations, AMPs can span a phospholipid membrane. The membrane phosphate head group is represented by spheres. Phosphate head groups from POPC that are in proximity to the peptide are shown in tan and phosphate head groups from then anionic POPG are  shown in orange. The AMP can destabilize biological membranes by sequestering waters and charged phosphate head groups into the hydrophobic core of the membrane.
Structure Characterization of Bio-Molecules:: Bio-molecules  can range from  proteins and peptides through to secondary metabolites and toxins. Our group has focused on structural and dynamic characterization of proteins and peptides. Current investigations involve characterization of a 15N and 15N/13C labelled toxic peptide from the Northern Short Tail Shrew that is 100 time more potent than scorpion venom. .	Peptide that composes scorpion venom
NMR Methodology Development: Many of the projects are focused on NMR spectroscopic method development. This ranges from multiple quantum spectral acquisition and analysis of orientationally ordered molecules [J. Mag. Res. (2002) 155, 251-256, NMR of Ordered Liquids, Burnell, E.E and de Lange, C.A. editors. Kluwer Academic, Dordrecht, The Netherlands], DOSY analysis for molecular mass distribution of complex polysaccharides [Biomacromolecules (2006) 7, 2368-2376], quantitative analysis of complex biofluids, and metabolnomics. Of particular interest is the work that Dr. Nadine Merkley is pursuing - profiling of whole cell algae samples with HRMAS for quality assurance/quality control (QA/QC). As part of NRCs Carbon Capture Flagship we are assisting with identifying lipids, carbohydrates and high-value natural products from various algae strains that will be utilized within a carbon-capture process.

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