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
Vortex fluidic mediated chemical transformations. This project aims to develop a continuous flow vortex fluidic device (VFD) for chemical and biochemical transformations. Vortex fluidic devices should lead to cleaner and faster ways of preparing complex molecules. Depending on the VFD’s operating parameters, including applying field effects such as Faraday waves, plasmas and light sources, reactions could have higher yields and selectivity than traditional batch processing. This will be translat ....Vortex fluidic mediated chemical transformations. This project aims to develop a continuous flow vortex fluidic device (VFD) for chemical and biochemical transformations. Vortex fluidic devices should lead to cleaner and faster ways of preparing complex molecules. Depending on the VFD’s operating parameters, including applying field effects such as Faraday waves, plasmas and light sources, reactions could have higher yields and selectivity than traditional batch processing. This will be translated into molecular assembly line syntheses in a single unit or a series. Such syntheses should provide a versatile toolbox for molecular transformations, under continuous flow conditions where scalability is addressed upfront. This will be attractive to industry and minimise effects on the environment.Read moreRead less
Biosynthetic LEGO: enzymatic redesign to produce new vancomycin analogues. This project aims to uncover the reengineering potential of the biosynthetic machinery that produces glycopeptide antibiotics by advancing our understanding of how the core peptide production line functions. Natural product biosynthesis often produces complex peptide structures, with one important example being the glycopeptide antibiotics. This project expects to generate new knowledge about enzymatic peptide biosynthesi ....Biosynthetic LEGO: enzymatic redesign to produce new vancomycin analogues. This project aims to uncover the reengineering potential of the biosynthetic machinery that produces glycopeptide antibiotics by advancing our understanding of how the core peptide production line functions. Natural product biosynthesis often produces complex peptide structures, with one important example being the glycopeptide antibiotics. This project expects to generate new knowledge about enzymatic peptide biosynthesis using a highly interdisciplinary approach and previously developed tools. The anticipated outcomes of this project will be an enhanced understanding of how such complex peptide biosynthesis is performed, which is knowledge vital for future efforts to reengineer such biosynthetic peptide assembly lines as a series of modular LEGO blocks to produce new bioactive peptides.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.
Development and application of new peptide ligation methods for the synthesis and structure-function studies of glycoproteins. Novel synthetic technologies will be developed in this project to facilitate the preparation of glycoproteins, which are of widespread biological and therapeutic interest. These methods will enable the preparation of pure glycoproteins for detailed biochemical and functional studies eventually leading to therapeutic and diagnostic applications.
New peptide ligation technology for the rapid assembly of modified proteins. The project aims to develop novel technologies to enable the synthesis of modified proteins that are of widespread biological and therapeutic interest. More than 70 per cent of all human proteins are modified with a range of functionalities after translation from the ribosome. Although these modifications are of crucial importance for biological activity, characterising the effect of a given modification on function is ....New peptide ligation technology for the rapid assembly of modified proteins. The project aims to develop novel technologies to enable the synthesis of modified proteins that are of widespread biological and therapeutic interest. More than 70 per cent of all human proteins are modified with a range of functionalities after translation from the ribosome. Although these modifications are of crucial importance for biological activity, characterising the effect of a given modification on function is difficult due to problems in obtaining the protein in pure form. The goal of this project is to develop a peptide ligation methodology to access pure modified proteins in a rapid manner through the exploitation of a new reaction recently discovered in our laboratory. The project plans to explore the scope and mechanism of the new reaction as well as its application in the total chemical synthesis and structure-function studies of important modified proteins.Read moreRead less