Nettles & toxic toupees: the molecular weaponry of venomous caterpillars. This project aims to investigate the structure, function and evolution of peptide toxins in venoms made by caterpillars in superfamily Zygaenoidea. Caterpillars in this group are covered in spines that inject pain-causing venoms, and this protects them from vertebrate and invertebrate predators. This project will test if peptides in this venom cause pain by pharmacological modulation of mammalian ion channels and signallin ....Nettles & toxic toupees: the molecular weaponry of venomous caterpillars. This project aims to investigate the structure, function and evolution of peptide toxins in venoms made by caterpillars in superfamily Zygaenoidea. Caterpillars in this group are covered in spines that inject pain-causing venoms, and this protects them from vertebrate and invertebrate predators. This project will test if peptides in this venom cause pain by pharmacological modulation of mammalian ion channels and signalling receptors, and if they have insecticidal properties. The first three-dimensional structures of caterpillar venom peptides will also be solved. Genomes of representatives of two different zygaenoid families will be produced, and genomic techniques will be used to elucidate how venom use evolved at the molecular level.Read moreRead less
Developing a multicomponent platform for targeted gene delivery. Gene delivery systems are important tools in biological research and offer many exciting future prospects. Delivering gene material is very difficult in practice: rapid deterioration, poor cell uptake, and reaching the right tissue and cell types are major obstacles. Ways to overcome each barrier individually have been suggested in existing research but these components have not yet been combined in a single solution, which this pr ....Developing a multicomponent platform for targeted gene delivery. Gene delivery systems are important tools in biological research and offer many exciting future prospects. Delivering gene material is very difficult in practice: rapid deterioration, poor cell uptake, and reaching the right tissue and cell types are major obstacles. Ways to overcome each barrier individually have been suggested in existing research but these components have not yet been combined in a single solution, which this project will tackle. This proposal aims to create a technology to stabilise and deliver active gene material to target cells. The gene delivery tool developed in this project will advance biological research greatly with many potential future applications.Read moreRead less
Development of a multicomponent delivery system for oligonucleotides. Gene therapy has the ability to prevent faulty genes from causing disease, however the ability to deliver genetic material into specific cells remains a major barrier. Our research will overcome this hurdle by generating systems that are superior to existing technologies.
The mechanism of membrane disruption by antimicrobial peptides. Bacterial resistance to antibiotics is a growing crisis in modern medicine. Antibacterial peptides from Australian frogs represent a new class of potent and selective antibacterial agents. Understanding how these peptides kill bacteria but not vertebrate cells could lead to the design of new drugs for pharmaceutical and/or clinical purposes.
Novel conotoxins that target ion channels and receptors. This project will discover peptides from cone snail venom that are potential drug candidates. The project will expand our knowledge of these biological active peptides and their mode of action. It will also protect key molecules through patent applications, providing a competitive edge for Australian biotechnology.
Toxins from Down Under: Novel tools to understand and modulate ion channels. Venoms are complex secretions containing biologically active components that have evolved over millions of years to specifically target the nervous systems of predators and prey. Two novel classes of toxins from snake and plant venoms that act on voltage-gated sodium channels, key proteins that regulate neuronal excitability, were recently identified by the research team. The project aims to develop and apply state-of-t ....Toxins from Down Under: Novel tools to understand and modulate ion channels. Venoms are complex secretions containing biologically active components that have evolved over millions of years to specifically target the nervous systems of predators and prey. Two novel classes of toxins from snake and plant venoms that act on voltage-gated sodium channels, key proteins that regulate neuronal excitability, were recently identified by the research team. The project aims to develop and apply state-of-the-art chemical, structural and biological techniques to unravel the molecular mechanisms through which these novel toxin classes act at their targets. Insights gained from this project will help identify and develop novel channel-modulating molecules that may have applications as neuroscience tools, diagnostics or drugs.Read moreRead less
Gain from pain: new tools from venomous animals for exploring pain pathways. This project aims to explore animal venoms for new pain-causing toxins, to determine their structure and mechanism of action. Many venomous animals use their venom defensively and envenomation is frequently associated with rapid and often excruciating pain. In most cases the molecular mechanisms by which they achieve this is unknown. Using biochemical, pharmacological and biophysical techniques, this project expects to ....Gain from pain: new tools from venomous animals for exploring pain pathways. This project aims to explore animal venoms for new pain-causing toxins, to determine their structure and mechanism of action. Many venomous animals use their venom defensively and envenomation is frequently associated with rapid and often excruciating pain. In most cases the molecular mechanisms by which they achieve this is unknown. Using biochemical, pharmacological and biophysical techniques, this project expects to uncover toxins that employ new mechanisms of pain signalling, leading to new insights into pain physiology.Read moreRead less
Conotoxin diversification and evolution of venom peptides in cone snails. The marine snails of the genus Conus have evolved one of the most complex venoms that has emerged as a rich source of novel bioactive peptides. However, < 0.1% of their true potential has been characterised to-date. Using advanced genomic, proteomic, structural and pharmacological approaches pioneered in our laboratory, this study will decipher how conotoxin diversification from ancestral worm hunters facilitated the shift ....Conotoxin diversification and evolution of venom peptides in cone snails. The marine snails of the genus Conus have evolved one of the most complex venoms that has emerged as a rich source of novel bioactive peptides. However, < 0.1% of their true potential has been characterised to-date. Using advanced genomic, proteomic, structural and pharmacological approaches pioneered in our laboratory, this study will decipher how conotoxin diversification from ancestral worm hunters facilitated the shift in diet to modern fish and mollusc hunting species by determining the evolutionary trajectories of positively selected conotoxins. Investigation of the structure and function of these highly optimised venom peptides will provide new research tools and potential leads to new pharmaceuticals and agrochemicals.Read moreRead less
Compressing small peptides for cell absorption. This project aims to understand how to make small structured peptides cell-permeable. Short peptides matching bioactive protein surfaces have no structure in water and do not enter cells, where most biological reactions occur. This project will compress peptides into very small coiled structures and systematically vary cyclic restraints, physicochemical properties and location of components to increase cell uptake by different mechanisms. An expect ....Compressing small peptides for cell absorption. This project aims to understand how to make small structured peptides cell-permeable. Short peptides matching bioactive protein surfaces have no structure in water and do not enter cells, where most biological reactions occur. This project will compress peptides into very small coiled structures and systematically vary cyclic restraints, physicochemical properties and location of components to increase cell uptake by different mechanisms. An expected outcome is new knowledge for predicting structures that make peptides cell-permeable without membrane damage. A new capacity to rationally downsize proteins to small, cell-permeable, structured peptides is anticipated to permit many new biological and industrial applications.Read moreRead less
Development of potent and specific modulators of the human sodium channel Nav1.7. There are few effective drugs available for the treatment of chronic pain. This team recently discovered that spider venoms are a rich source of inhibitors of Nav1.7, a new target for anti-pain drugs. The goal of this project is to develop potent blockers of Nav1.7 that can be used to critically assess the role of this ion channel in mediating pain.