Current Projects
Chemical Control of novel toxins from Australia’s venomous creatures
Many organisms including insects, snakes, spiders, molluscs, frogs, fish and some mammalian species have evolved venom as either a defence mechanism or as a primary weapon for the capture of their prey. The plethora of biologically active molecules that constitute venom is used to disrupt or control essential organ systems in the envenomed animal and most venomous species present an incredibly rich and yet untapped polypeptide (ie toxins) libraries – based on recent proteomic analyses in our labs we estimate that the cone snails alone have greater than 1,000,000 uncharacterised bioactive peptides. These toxins target different ion channels and their subtypes and possess highly conserved cysteine frameworks with multiple disulfide bonds that give rise to well-defined three-dimensional structures. Each venom is composed of a complex mixture of neurotoxins that target GPCRs, ion-channels, proteases and transporters that act in either the central or peripheral nervous systems. Their high degree of protease stability plus high potency combined with exquisite selectivity provides a valuable source of research tools for pharmacologists, neurochemists and physiologists, often with significant applications in drug discovery. Unfortunately, the current rate of discovery and characterisation from venoms does not match the expanding rate of new drug targets from the human genome and screening technologies to under their broad physiology and pharmacology. Our current research is focused on developing new chemistry and technologies to overcome these deficits.
Projects include:
➢ New methods using mass spectrometry and gene technology to accelerate de novo sequence determination of toxin sequences
➢ New selenochemistry to accelerate regioselective control of toxin folding
➢ New fast and efficient chemistry to enhance the development of structure activity relationships
➢ New cyclisation strategies to enhance toxin stability and drug delivery
➢ Design and synthesis of water soluble fluorescent tags suitable for conjugation (eg using ‘click’ chemistry or metathesis) with appropriately tagged toxins
➢ Toxin drug development
Milk Proteomics
Various treatments of milk and the subsequent storage of the product at room temperature results in substantial changes to the milk proteins the molecular basis of which are poorly understood. These changes have significant effects on the stability and nutritive value of the milk. Previous research by others has been carried out on the most obvious chemical changes which occur during heating, namely the denaturation of β-lactoglobulin and its subsequent interaction with κ-casein and formation of lactose adducts of proteins, the first step in the Maillard series of reactions. The use of proteomic techniques to characterize milk proteins is a relatively recent approach that we have pioneered to characterise post-translational modifications of bovine, camel and human milk proteins. Our recent research using a proteomic approach has shown that major chemical changes including deamidation, and formation of non-disulfide-linked protein oligomers could be observed after heat treatments of various milks. Such reactions have attracted very limited attention in the past but may play a major role in the stability of UHT milk and milk powders stored for long periods. Current research is focused on uncovering the specific chemical modifications that have occurred using proteomics-mass spectrometric approaches and developing a molecular level understanding of changes that are chemically derived.
Understanding Pain pathways using venom peptides - peptide synthesis of novel venom peptides and their analogues to identify new pain pathways - Read More -NOW!!
Also see Grants Success