The aims of our research program are 1) to study the structure and membrane interaction of biologically and pharmaceutically important proteins in their native environment using solid state NMR and complementary techniques such as solution state NMR, circular dichroism (CD), oriented CD (OCD), and differential scanning calorimetry (DSC) and 2) to use this combined information to understand how these biomolecules function. This knowledge is critical for understanding fundamental biological processes and ultimately designing and developing new anti-infective agents and medical devices.
Research focuses on two primary areas:
A. ANTIMICROBIAL PEPTIDES: MECHANISM OF ACTION TO DESIGN BETTER ANTIBIOTICS AND MEDICAL DEVICES
With the increasing prevalence of antibiotic resistance, many researchers are working towards developing new sustainable antibiotics , by investigating the mechanisms of action of different types of bactericidal agents. Two classes of compounds that have attracted a lot of interest are cationic antimicrobial peptides and lipopeptides, since they display few resistance effects. Our past work has focused on studying the structure/function relationship of two cationic antimicrobial peptides from amphibians: aurein 2.2 and aurein 2.3 from Australian Southern Bell Frogs Litoria aurea, as well as the lipopeptides daptomycin (collaboration with Cubist Pharmaceuticals, USA) and MX-2401 (collaboration with Migenix/Biowest Pharma). Current work in the lab examines novel peptides derived from aurein 2.2, as well as ways to conjugate these to polymers to minimize toxicity.
B. U24 MEMBRANE PROTEIN FROM HHV6 AND HHV7: UNDERSTANDING KEY ASPECTS OF MULTIPLE SCLEROSIS THROUGH STRUCTURE.
Human Herpes Virus type 6 (HHV-6) and type 7 (HHV-7) are two of a family of eight human herpes viruses. Recently, HHV-6 and HHV-7 have been found to be associated with Multiple Sclerosis (MS) and immunodeficiency-related diseases. U24 is a 10 kDa membrane-anchored protein from HHV-6A and HHV-6B (two closely related viruses in the Roseolovirus family), as well as HHV-7. U24 from HHV-6A shares a 7 amino acid sequence identity with myelin basic protein (MBP), a non-viral protein which is essential for preserving the integrity of myelin sheaths in the central nervous system (CNS) and which has been implicated in MS. This common segment is believed to be essential for recognition by T-cells. We have studied the interaction of U24 with a number of binding partners, such as Fyn-SH3, and WW domains.