Research Interests: Antimicrobial peptides (AMPs) are naturally-occurring cationic peptides (<100 amino acid residues) that have been shown to induce selective lytic activity in membranes. Protegrin-1 (PG-1) is an 18- residue AMP which forms an anti-parallel ß-hairpin structure in solution that is stabilized by two disulfide bonds. It was originally thought that electrostatic attraction of the cationic peptide side chains to the bacterial membrane anionic head groups was primarily responsible for selectivity. Antimicrobial peptides disrupt bacterial membranes in much lower concentrations then mammalian membranes. Recent work has shown that more subtle characteristics of membrane composition, such as fluidity and acyl chain length, affects the activity of PG-1. Cholesterol is a naturally occurring sterol found in eukaryotic cell membranes, and effects both the fluidity of the membrane as well as the acyl chain length.
I will explore the effects of cholesterol on the activity of PG-1. Cholesterol, along with other sterols and sterol-like molecules, is commonly found in eukaryotic membranes and causes the fluidity to decrease and the hydrophobic region to expand. This experimental system will allow us to determine the importance of cholesterol in membranes with respect to AMP activity. This is important to examine because of the prevalence of cholesterol and other sterols in eukaryotic membranes relative to prokaryotic membranes. This system will allow for better understanding of the selectivity of AMPs to membranes.