With the support of a CAREER award from the Organic and Macromolecular Chemistry Program at the National Science Foundation, Professor Myriam Cotten of Pacific Lutheran University will investigate structure-function-dynamics relationships in amphipathic cationic antimicrobial peptides, important peptides belonging to a large family of biomolecules active at interfaces. The long-term goal is to identify common principles that will facilitate the design of pharmaceuticals with broad-spectrum antibacterial activity, minimum induction of bacterial resistance, and low toxicity to mammalian cells. A bottleneck in this area of research is the lack of atomic level information on peptide-lipid interactions. Professor Cotten's main objective is to characterize the secondary structures and dynamics of selected antimicrobial peptides in the presence of lipids. This knowledge will be used to identify factors optimizing specific molecular interactions, initially at cell membranes, that are directly related to peptide function and mode of action. Biochemical, biophysical, and spectroscopic methods will be used to synthesize and purify selected antimicrobial peptides; and to compare their atomic level structures, molecular interactions with lipids, and dynamics under physiologically-relevant conditions to advance our understanding of molecular recognition, specificity, mode of action, and potency. Piscidins, the selected peptides, will be incorporated in aligned, hydrated lipid bilayers and subjected to solid-state nuclear magnetic resonance techniques. Specific parameters relevant to biological function will be tested.
With the support of a CAREER award, interdisciplinary research on important antimicrobial peptides will provide results that will feed a larger body of knowledge aimed at improving our fundamental understanding of how these peptides recognize membranes and initiate their activities on different types of cells. Broader impacts of the proposed activity are primarily the high quality science education which will be offered to a diverse research group. This team will include college and pre-college students from underrepresented groups, a future high school teacher, and a postdoctoral fellow. All project participants will engage in rigorous scientific inquiry and delightful discovery. They will actively contribute to the proposed research, travel to national user facilities equipped with state-of-the-art instrumentation, and present results at local and national meetings. This program will help inspire students for professionally and personally rewarding scientific careers that will contribute to continued vitality of the sciences and workforce.
