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
Defining a new family of sodium channel accessory proteins. Voltage-gated sodium channels are key proteins that function as multi-subunit complexes to regulate neuronal excitability. The project aims to investigate the structure and function of a novel family of accessory subunits by utilizing a class of toxins, derived from the giant Australian stinging tree, that directly binds to these proteins to modulate sodium channel function. The project aims to generate significant new knowledge on the ....Defining a new family of sodium channel accessory proteins. Voltage-gated sodium channels are key proteins that function as multi-subunit complexes to regulate neuronal excitability. The project aims to investigate the structure and function of a novel family of accessory subunits by utilizing a class of toxins, derived from the giant Australian stinging tree, that directly binds to these proteins to modulate sodium channel function. The project aims to generate significant new knowledge on the function of sodium channels as multi-protein complexes. Expected outcomes of this project include development of novel channel-modulating molecules that may have applications as neuroscience tools to address fundamental questions about ion channel function and biology.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
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
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
Single-session Introduction of Mutations in Parallel Lines (SIMPL). This project aims to develop a novel method for markedly accelerating production of genetically modified mice, which are a key 'tool' for studying biological processes and diseases. The work plans to take CRISPR, the latest gene-editing technique, to the next level by developing a novel CRISPR-based method to generate different mouse strains with distinct variations of the same gene sequences, at a fraction of the present cost a ....Single-session Introduction of Mutations in Parallel Lines (SIMPL). This project aims to develop a novel method for markedly accelerating production of genetically modified mice, which are a key 'tool' for studying biological processes and diseases. The work plans to take CRISPR, the latest gene-editing technique, to the next level by developing a novel CRISPR-based method to generate different mouse strains with distinct variations of the same gene sequences, at a fraction of the present cost and time. This project should overcome a major barrier to studying gene function with unprecedented detail, thereby opening new avenues for future research into biological processes. Thus, the outcomes from this project should impact on the entire field of biomedical research, and advance Australia's biotech industry.Read moreRead less
Carbon Molecular Sieve Membranes for Organic Solvent Separation. Directly addressing the pressing challenge of organic solvent separation faced by numerous industries, the project aims to develop molecular sieve membranes with outstanding selectivity and solvent tolerance by constructing zeolite-carbon mixed matrix membrane via incorporating zeolite nanosheets into carbon materials. The project expects to generate advanced knowledge of nanosheet synthesis, membrane fabrication and selective mole ....Carbon Molecular Sieve Membranes for Organic Solvent Separation. Directly addressing the pressing challenge of organic solvent separation faced by numerous industries, the project aims to develop molecular sieve membranes with outstanding selectivity and solvent tolerance by constructing zeolite-carbon mixed matrix membrane via incorporating zeolite nanosheets into carbon materials. The project expects to generate advanced knowledge of nanosheet synthesis, membrane fabrication and selective molecule transport. The membranes developed in the project have great potentials for improving the production capacity and sustainability of Australian industries, e.g., pharmaceutical manufacturing, bioethanol production and petroleum refining, providing significant economic and environmental benefits to Australia.Read moreRead less
Crystal engineering of membranes for chiral separation . This project addresses the urgent challenge of chiral separation in the manufacturing of pharmaceuticals and agrochemicals by creating a new class of membranes produced by engineering functionalised porous framework crystals. This project expects to generate new knowledge regarding how membrane chemistry and architecture can be used to achieve highly selective, fast chiral molecule transport. The expected outcomes of the project include ne ....Crystal engineering of membranes for chiral separation . This project addresses the urgent challenge of chiral separation in the manufacturing of pharmaceuticals and agrochemicals by creating a new class of membranes produced by engineering functionalised porous framework crystals. This project expects to generate new knowledge regarding how membrane chemistry and architecture can be used to achieve highly selective, fast chiral molecule transport. The expected outcomes of the project include new membrane compositions, design principles, fabrication techniques, and proof-of-concept production of scalable, high-performance composite membranes. This project should produce significant economic and environmental benefits in the development of advanced membranes, pharmaceuticals, and agrochemicals.Read moreRead less
Highly Efficient Nanomotors for Autonomous Cell Recognition and Isolation. This project aims to develop next-generation self-driven nanomotors capable of long-range motion with highly controlled directionality for cell recognition, transportation and separation in complex biological environments, to allow autonomous and seamless cell sorting with high accuracy. The anticipated goal of this project is to advance the field of nanotechnology and advanced manufacturing with potential to support new ....Highly Efficient Nanomotors for Autonomous Cell Recognition and Isolation. This project aims to develop next-generation self-driven nanomotors capable of long-range motion with highly controlled directionality for cell recognition, transportation and separation in complex biological environments, to allow autonomous and seamless cell sorting with high accuracy. The anticipated goal of this project is to advance the field of nanotechnology and advanced manufacturing with potential to support new applications and to value-add Australia’s advanced manufacturing industry, presenting new opportunities for Australian MedTech industries with innovative, disruptive technologies to address its unique needs and to claim Australia’s position within the competitive global market.Read moreRead less
A microfluidic approach to study the mechanobiology of ageing blood vessels. This project aims to study the effect of the stiffening of ageing arteries in endothelial cells. It explores the changes that occur in endothelial cells using a unique microfluidic technology with tuneable wall stiffness to mimic the biophysical and biochemical properties of ageing arteries. The expected outcome is the identification of the cellular mechanisms that control endothelial responses to arterial stiffening. T ....A microfluidic approach to study the mechanobiology of ageing blood vessels. This project aims to study the effect of the stiffening of ageing arteries in endothelial cells. It explores the changes that occur in endothelial cells using a unique microfluidic technology with tuneable wall stiffness to mimic the biophysical and biochemical properties of ageing arteries. The expected outcome is the identification of the cellular mechanisms that control endothelial responses to arterial stiffening. This should provide the fundamental knowledge required to assist in the development of new therapies to tackle age-related conditions such as cardiovascular disease and dementia.Read moreRead less