Current Projects

Transcriptomic Proteomic and Venomic Discovery and Chemical Synthesis and 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 advance proteomic analyses in our labs we estimate that the cone snails alone have greater than 1,000,000 uncharacterised bioactive peptides called conotoxins. These toxins 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. Importantly, next generation sequencing and advanced mass spectrometry have sped up the discovery process and we are well positioned to find new drug targets using high-throughput screening technologies that will enable us to understand the broad physiology and pharmacology of these peptidic molecules. Our current research is focused on developing new chemistry to match the discovery and characterisation.

Projects include:

  • New methods using mass spectrometry and gene technology to accelerate discovery of toxin sequences
  • Discovery of peptide toxins that target specific pain receptors
  • New regioselective synthesis and selenochemistry to accelerate 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
  • Development of therapeutic peptide dendrimers to understand Gut-CNS and pain signalling
  • Oxytocin and vasopressin research and development of lead molecules for breast cancer