Structure and Function of novel Direct Antimicrobial and Immunomodulatory Peptides
With the advent of antibiotic resistance, it has become increasingly important to develop alternatives to currently used antibiotics. In our laboratory, we have investigated the structure and function of a number of potentially interesting drug candidates. In the proposed project, we will design and develop a new generation of peptides derived from the two peptides mentioned above. The aim will be to find candidate peptides which display immune regulatory activity and direct antimicrobial activity. To accomplish this goal, we will utilize many of the design rules we have developed over the years of research in this area [2-5]. Once we have identified a number of potential candidates, we will synthesize and purify the peptides. In collaboration with the Hancock laboratory, we will test the activity of these peptides against a host of Gram positive and Gram negative bacteria. Next, we will characterize the secondary structure of the active peptides by circular dichroism and determine their three dimensional structure by solution state nuclear magnetic resonance (NMR). We will also study how these peptides interact with model membranes using a range of techniques, such as oriented circular dichroism, differential scanning calorimetry, and solid state NMR.
The student will learn to: design novel peptides which have the potential to be good antimicrobial and immunomodulatory peptides, synthesize peptides using an automated peptide synthesizer, isolate and purify the peptides using protocols already in place (the purification will require the use of an HPLC); learn about the different assays used to determine antimicrobial and immunomodulatory activity; determine the secondary structure of the peptides using circular dichroism; determine the structure of the most active peptide using solution state NMR techniques; determine peptide-lipid interactions, using a range of biophysical techniques, such as oriented CD, differential scanning calorimetry, etc