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
Structure and function of predatory and defensive venoms in cone snails. This project aims to investigate newly-discovered cone snail venoms to accelerate the search for novel bioactive peptides. It was recently discovered that cone snails can rapidly and reversibly switch between distinct venoms in response to predatory or defensive stimuli, implying that defensive and predatory venoms have evolved under separate selection pressures. The project plans to obtain separate predatory and defensive ....Structure and function of predatory and defensive venoms in cone snails. This project aims to investigate newly-discovered cone snail venoms to accelerate the search for novel bioactive peptides. It was recently discovered that cone snails can rapidly and reversibly switch between distinct venoms in response to predatory or defensive stimuli, implying that defensive and predatory venoms have evolved under separate selection pressures. The project plans to obtain separate predatory and defensive venoms and venom duct tissue from individual cone snails to compare and contrast the structure and function of conotoxins evolved for predation versus those evolved for defence, to elucidate the structure and function of these important classes of bioactive peptides.Read moreRead less
A new class of sodium channel toxin from ant venoms . Ants are diverse and ubiquitous and the ability of certain species to sting is familiar to many of us. Yet we know remarkably little about the chemistry underlying these stings. We recently discovered that the venoms of ants, including common Australian species, harbour a novel and unique class of sodium channel toxins. Building on this discovery, the aim of this project will be to perform an in-depth characterisation of the effects of these ....A new class of sodium channel toxin from ant venoms . Ants are diverse and ubiquitous and the ability of certain species to sting is familiar to many of us. Yet we know remarkably little about the chemistry underlying these stings. We recently discovered that the venoms of ants, including common Australian species, harbour a novel and unique class of sodium channel toxins. Building on this discovery, the aim of this project will be to perform an in-depth characterisation of the effects of these toxins on sodium channels and to uncover the diversity and breadth of this toxin class in ant venoms. The outcome of this project will be novel insights into the chemistry of ant venoms and new insights into sodium channel function.Read moreRead less
Unravelling the molecular diversity and evolution of centipede venoms. The project intends to improve understanding of venom evolution in centipedes. Venoms have emerged as a rich source of pharmacological tools with potential for development into therapeutics and bioinsecticides. However, venoms-based discovery has been limited by the narrow taxonomical range of animals studied, with many groups of venomous animals overlooked. One such group is centipedes, whose venoms contain diverse toxins th ....Unravelling the molecular diversity and evolution of centipede venoms. The project intends to improve understanding of venom evolution in centipedes. Venoms have emerged as a rich source of pharmacological tools with potential for development into therapeutics and bioinsecticides. However, venoms-based discovery has been limited by the narrow taxonomical range of animals studied, with many groups of venomous animals overlooked. One such group is centipedes, whose venoms contain diverse toxins that differ between taxa. This project aims to provide an insight into centipede venom evolution, and how it might be constrained by venom-gland morphology. This study seeks to contribute to our understanding of protein evolution and direct biodiscovery efforts around centipede venom.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
Engineering peptides into superglues selective for target proteins. This project aims to discover how to create long-acting peptides for future research tools, drugs, biosensors and diagnostics. Peptides are currently viewed by the general community as injectable performance-enhancing drugs which are difficult to detect because they don't last very long. However, peptides have many potential benefits that are difficult to obtain because of their short durations of action. This project aims to de ....Engineering peptides into superglues selective for target proteins. This project aims to discover how to create long-acting peptides for future research tools, drugs, biosensors and diagnostics. Peptides are currently viewed by the general community as injectable performance-enhancing drugs which are difficult to detect because they don't last very long. However, peptides have many potential benefits that are difficult to obtain because of their short durations of action. This project aims to develop ways of engineering peptide shapes into nanoscale superglues that stick more tightly but selectively to their target proteins, thereby extending their durations of action. Technology for engineering superglues would produce proof of concept and prototypes for future research tools, drugs, diagnostics and biosensors.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
Venom-derived blood-brain-barrier shuttles. This project aims to discover new venom peptides capable of crossing the blood-brain barrier and to develop non-toxic peptide-based brain delivery systems. It addresses long-standing challenges and knowledge gaps in the delivery of macromolecules across biological barriers. Expected outcomes include an improved understanding of the strategies nature exploits to reach targets in the brain, mechanistic pathways to cross biological membranes, and innovati ....Venom-derived blood-brain-barrier shuttles. This project aims to discover new venom peptides capable of crossing the blood-brain barrier and to develop non-toxic peptide-based brain delivery systems. It addresses long-standing challenges and knowledge gaps in the delivery of macromolecules across biological barriers. Expected outcomes include an improved understanding of the strategies nature exploits to reach targets in the brain, mechanistic pathways to cross biological membranes, and innovative discovery and chemistry strategies to advance fundamental research across the chemical and biological sciences. Anticipated benefits include technological innovations relevant to Australia’s biotechnology sector and enhanced capacity for cross-disciplinary collaboration.Read moreRead less
A new source of bivalent molecules from nature. This project aims to describe a new class of naturally occurring multivalent molecules termed secreted cysteine-rich repeat proteins (SCREPs). Multivalency is a key feature of molecular interaction in biology, underlying the high specificity and potency found in many proteins. Focusing on bivalent peptides, the project will generate a database of bioactive SCREPs with similarity to known bioactive peptides, and develop new recombinant methods for t ....A new source of bivalent molecules from nature. This project aims to describe a new class of naturally occurring multivalent molecules termed secreted cysteine-rich repeat proteins (SCREPs). Multivalency is a key feature of molecular interaction in biology, underlying the high specificity and potency found in many proteins. Focusing on bivalent peptides, the project will generate a database of bioactive SCREPs with similarity to known bioactive peptides, and develop new recombinant methods for their production. The project will use advanced nuclear magnetic resonance spectroscopy to characterise members of this new class, providing new insights into the design of bivalent and multivalent peptides and establishing a new source of molecules with applications in the rapidly growing biotechnology sector.Read moreRead less
Autocyclases: A new class of self-cyclising proteins. The biotechnology sector is emerging as an important economic strength in Australia. While the improved efficacy and selectivity of biomolecules has seen them emerge as alternatives to existing chemicals in health and agriculture, the stability of biomolecules remains a major limiting factor. A general strategy for improving protein stability is by joining the ends of the peptide chain in a cyclisation reaction. While a wide range of cyclic p ....Autocyclases: A new class of self-cyclising proteins. The biotechnology sector is emerging as an important economic strength in Australia. While the improved efficacy and selectivity of biomolecules has seen them emerge as alternatives to existing chemicals in health and agriculture, the stability of biomolecules remains a major limiting factor. A general strategy for improving protein stability is by joining the ends of the peptide chain in a cyclisation reaction. While a wide range of cyclic peptides and proteins are being developed in Australia and around the world, the cyclisation reaction presents a significant challenge. In this proposal we detail a novel method for protein cyclisation as a general, low-cost and green production method for making a diverse range of biomolecules. Read moreRead less