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
Expanding access to modified proteins via a novel semi-synthetic platform. This project aims to address a critical knowledge gap in understanding how post-translational modifications modulate the structure and activity of proteins. By developing an innovative semi-synthetic platform to produce pure proteins inaccessible by existing methods, the project will reveal how natural protein modifications influence structure and function. Expected outcomes include the delivery of breakthrough technologi ....Expanding access to modified proteins via a novel semi-synthetic platform. This project aims to address a critical knowledge gap in understanding how post-translational modifications modulate the structure and activity of proteins. By developing an innovative semi-synthetic platform to produce pure proteins inaccessible by existing methods, the project will reveal how natural protein modifications influence structure and function. Expected outcomes include the delivery of breakthrough technologies for accessing modified proteins for a range of applications in academia and industry, as well as the generation of new knowledge in the fields of chemistry and biology. The project will lead to the training of interdisciplinary early career researchers and has the potential to benefit Australia’s biotechnology sector.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
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
Novel green scalable chemical peptide synthesis and enzyme immobilization. The Project aims to address the critical issue of developing green processes for the chemical production of peptides including on an industrial scale. It will use unique, biocompatible solid supports that have been invented by our partner SpheriTech Ltd together with other reagents to allow synthesis to be conducted in water rather than toxic organic solvents. Expected outcomes of the Project include an international part ....Novel green scalable chemical peptide synthesis and enzyme immobilization. The Project aims to address the critical issue of developing green processes for the chemical production of peptides including on an industrial scale. It will use unique, biocompatible solid supports that have been invented by our partner SpheriTech Ltd together with other reagents to allow synthesis to be conducted in water rather than toxic organic solvents. Expected outcomes of the Project include an international partnership in highly efficient environmentally-friendly assembly of peptides and of their analogues by both solid phase synthesis and immobilized enzyme-mediated ligation. The clear benefit will be the first novel, water-based, scalable green synthesis of peptides as biological probes and potential therapeutic agents.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
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
Understanding peptide bond formation in non-ribosomal peptide biosynthesis. This project aims to uncover the origins of selectivity exhibited by the biosynthetic machinery that produces non-ribosomal peptides through advancing our understanding of how the central peptide synthesis domain functions. This project intends to generate new knowledge about peptide biosynthesis using a highly interdisciplinary approach and essential tools that have been developed. The anticipated outcomes of this proje ....Understanding peptide bond formation in non-ribosomal peptide biosynthesis. This project aims to uncover the origins of selectivity exhibited by the biosynthetic machinery that produces non-ribosomal peptides through advancing our understanding of how the central peptide synthesis domain functions. This project intends to generate new knowledge about peptide biosynthesis using a highly interdisciplinary approach and essential tools that have been developed. The anticipated outcomes of this project will be an enhanced understanding of the structural basis for substrate selection exhibited during peptide synthesis, revealing the specificity code of these key domains. This knowledge is vital for future efforts to reengineer such biosynthetic peptide assembly lines to produce new bioactive peptides.Read moreRead less