Structural basis of receptor modulation by venom peptides
Animal venoms consist chiefly of a complex cocktail of small peptides, referred to as toxins. Most toxins are short polypeptide chains that adopt a globular fold, which is stabilised by multiple disulfide bonds. These cross-braces allow these molecules to withstand the harsh physiological environment of the prey they are injected into. In addition to being highly stable these peptides have over millions of years evolved to have exquisite selectivity and potency against various receptors in their prey. Venom peptides are therefore an excellent source of bio-molecules that can be used to study various biological process, with the potential to serve as lead molecules in developing therapeutics and diagnostics for a broad range of disease states. Classes of peptides currently studied and supported by external funding include analgesic peptides for the treatment of chronic pain and insecticidal peptides for agricultural applications.
The primary aim of current efforts in this area involve the structural studies of the voltage sensing domain (VSD) of voltage-gated ion channels. We primarily use NMR based methods to study the VSD in detergent micelles and more recently in lipid nano-disks. The long term aim is to provide a platform for both structure/function studies of voltage gating and for drug development against a wide range of voltage gated ion channels.