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
Bio-inspired molecular electronics: from nanoscience to nanotechnology. This project aims to investigate electron transport in naturally occurring peptides, while exploiting their electronic properties to promote the design and development of functional bio-inspired molecular electronic devices. Molecular electronics is at the forefront of international interdisciplinary research, with its significance and necessity stemming from the inevitable physical limitations of existing silicon-based elec ....Bio-inspired molecular electronics: from nanoscience to nanotechnology. This project aims to investigate electron transport in naturally occurring peptides, while exploiting their electronic properties to promote the design and development of functional bio-inspired molecular electronic devices. Molecular electronics is at the forefront of international interdisciplinary research, with its significance and necessity stemming from the inevitable physical limitations of existing silicon-based electronics. This project aims to establish a foundation to advance fundamental knowledge in this area, which will lead to the design and development of functional bio-inspired molecular electronic devices.Read moreRead less
Thioamide ligations: new technologies for peptide and protein synthesis. This project aims to develop novel amide-bond forming reactions for the chemical synthesis of peptides and proteins. New peptide ligation strategies, including an asparagine-based ligation and a residue-independent ligation will be developed that exploit the recent discovery of silver-promoted coupling reactions of thioamides. A novel late-stage, chemo-selective assembly of N-glycosylated asparagine residues in peptides and ....Thioamide ligations: new technologies for peptide and protein synthesis. This project aims to develop novel amide-bond forming reactions for the chemical synthesis of peptides and proteins. New peptide ligation strategies, including an asparagine-based ligation and a residue-independent ligation will be developed that exploit the recent discovery of silver-promoted coupling reactions of thioamides. A novel late-stage, chemo-selective assembly of N-glycosylated asparagine residues in peptides and proteins will also be developed. The outcomes of this research will lead to breakthroughs in synthetic methodologies for the assembly and functionalisation of peptides and proteins, thereby enabling access to a range of homogeneous, post translationally modified proteins though total chemical synthesis. These research outcomes will expand Australia's research capability and global competitiveness in the field of biotechnology, delivering significant benefits to the third largest manufacturing sector in Australia.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
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
Harnessing molecular strain for drug discovery and bioconjugation. Peptides and proteins are increasingly important therapies for the treatment of disease. Nevertheless, the synthesis and optimisation of these high-value compounds still relies primarily on technologies developed decades ago. There is a desperate need for modern strategies to unlock the full potential of peptides and proteins for diverse applications in drug discovery. This interdisciplinary research aims to develop new tools for ....Harnessing molecular strain for drug discovery and bioconjugation. Peptides and proteins are increasingly important therapies for the treatment of disease. Nevertheless, the synthesis and optimisation of these high-value compounds still relies primarily on technologies developed decades ago. There is a desperate need for modern strategies to unlock the full potential of peptides and proteins for diverse applications in drug discovery. This interdisciplinary research aims to develop new tools for the construction and modification of peptides and proteins by harnessing the energy in a unique class of strained molecules. A focus on peptide-based inhibitors of the proteasome, a critical target for modern cancer treatments, should provide future health and economic benefits for the Australian community.Read moreRead less
Understanding the mechanisms of peptide cyclisation. This project aims to identify, study, engineer and apply a new class of biocatalysts (called asparaginyl endopeptidase enzymes) as versatile tools for manufacturing of advanced therapeutics and bio-insecticides. The expected outcomes include fundamental new knowledge on the mechanism of action of these catalysts, an expanded toolbox for precision engineering of biomolecules and new strategies for production of high-value pharmaceuticals and cr ....Understanding the mechanisms of peptide cyclisation. This project aims to identify, study, engineer and apply a new class of biocatalysts (called asparaginyl endopeptidase enzymes) as versatile tools for manufacturing of advanced therapeutics and bio-insecticides. The expected outcomes include fundamental new knowledge on the mechanism of action of these catalysts, an expanded toolbox for precision engineering of biomolecules and new strategies for production of high-value pharmaceuticals and crop protecting agents. The project is significant because it will contribute to high value biotechnology and agricultural industries in Australia, with the potential for economic, environmental, training and societal benefits.Read moreRead less
Aquatic chemo-modulators: a novel source for potent molecular probes. This project aims to investigate peptides that modulate prey behaviour. Chemical signalling constitutes much of the language of life underwater. Certain cone snails evolved a hunting strategy, where they release potent peptides to modulate fish behaviour through yet unknown mechanisms. The snail then expands its mouth and eats the fish without resistance. This project will investigate the mechanisms at play using transcriptomi ....Aquatic chemo-modulators: a novel source for potent molecular probes. This project aims to investigate peptides that modulate prey behaviour. Chemical signalling constitutes much of the language of life underwater. Certain cone snails evolved a hunting strategy, where they release potent peptides to modulate fish behaviour through yet unknown mechanisms. The snail then expands its mouth and eats the fish without resistance. This project will investigate the mechanisms at play using transcriptomics, proteomics, peptide synthesis, behavioural pharmacology and nuclear magnetic resonance. This will advance the knowledge of aquatic chemo-modulators on a functional, structural and evolutionary level, and provide a source of molecular probes with unique pharmacology and applications in human physiology, developmental biology and aquacultures.Read moreRead less
Making peptides orally bioavailable. Bioactive peptides are exceptionally useful molecules, however to fully realise their exciting applications key limitations need to be overcome: they can't be delivered orally and they do not last long in the body. This project aims to develop a molecular tag that can dramatically enhance both the oral absorption and time in the body of a peptide. This will include identifying the key elements of the tag required for function, the breadth of peptide cargoes i ....Making peptides orally bioavailable. Bioactive peptides are exceptionally useful molecules, however to fully realise their exciting applications key limitations need to be overcome: they can't be delivered orally and they do not last long in the body. This project aims to develop a molecular tag that can dramatically enhance both the oral absorption and time in the body of a peptide. This will include identifying the key elements of the tag required for function, the breadth of peptide cargoes it can be applied to and the mechanisms underlying this technology. The outcomes of this project will facilitate the future development of peptides for biotechnology, pharmaceutical and veterinary applications.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