Overview
Proteins are the body's "molecular machines" and are central in the countless processes that maintain all living organisms. A protein's function comes about as a direct result of the particular features of its three-dimensional structure. Thus, we need to know this structure in order to properly understand how a protein works, as well as to design drugs to modify the protein's function to treat a disease. The details of this structure are too small to be seen directly, even in the most highly magnified images, and so we use techniques such as nuclear magnetic resonance (NMR) to determine the structure. Proteins that are embedded in the cell's membrane constitute about one-third of all proteins and are especially important in health and disease. These membrane-associated proteins pose unique technical challenges and relatively little is currently known about their structures. We use a combination of solution NMR in micelles and solid-state NMR in bilayers to characterize both protein structure and lipid interactions. We also use molecular dynamics simulation to augment the NMR work.
Lung surfactant proteins and peptides
Lung surfactant (LS) is a mixture of lipids and proteins that coats the airspaces in our lungs. Without it, we can't breathe: premature babies are commonly born with deficiencies in LS (this condition is called RDS) and need to be given exogenous LS in order to survive. People of any age who are very ill can sustain damage to their lung surfactant (ARDS). Unfortunately for these people, giving them exogenous LS does not seem to help them very much, likely in part because whatever conditions present in their lungs that lead to ARDS in the first place, rapidly inactivate any additional LS given to them.
Our work is aimed at understanding the molecular mechanisms of LS, particularly concerning the essential LS protein SP-B, as well as in designing "ARDS-resistant" peptides based on SP-B.
Peptides with antimicrobial activity
Although hundreds of peptide sequences with anti-bacterial/viral/fungal/tumor properties have been identified, we still have a very poor understanding of the molecular mechanisms by which they disrupt microbial cell function. Suitable antimicrobial peptides have much potential to address the current significant problem of bacterial (and other pathogen) resistance to small molecule antibiotics. The antimicrobial properties of these peptides appear to arise from their interactions with biomembranes. While a few peptides may just pass through the membrane on their way to an intra-cellular target, it appears that most antimicrobial peptides act by disrupting the membranes themselves.
Our work is focussed on elucidating the molecular mechanisms of antimicrobial peptide mechanism and specificity for pathogens over host cells.
Structure-based Design of Improved Therapeutics for Psoriasis
In collaboration with
NewLab Clinical Research Inc. we are performing structural studies aimed at design of improved therapies for psoriasis. This project is based in part on associations between psoriasis and particular genes that were identified in genetic studies of the
Newfoundland population.
For past projects, click here!
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