Ultrasensitive electrochemical biosensors. This project aims to develop novel proteins that can convert biochemical cues into electronic signals. Using protein engineering, this project will produce redox protein-based OFF switches. The project expects that the use of the OFF-switches (as opposed to ON switches) will simplify biosensor design and create a new class of sensory architectures. Integration of OFF-switch-based biosensors with an enzymatic signal amplification circuit is expected to y ....Ultrasensitive electrochemical biosensors. This project aims to develop novel proteins that can convert biochemical cues into electronic signals. Using protein engineering, this project will produce redox protein-based OFF switches. The project expects that the use of the OFF-switches (as opposed to ON switches) will simplify biosensor design and create a new class of sensory architectures. Integration of OFF-switch-based biosensors with an enzymatic signal amplification circuit is expected to yield ultrasensitive sensory systems with near-real-time response. The project will address a need for new technologies that enable collection of physiological and environmental information rapidly, and at low cost outside of the specialised laboratories.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
Genetic code expansion of a eukaryotic in vitro translation system. The genetic code programs biosynthesis of polypeptides with efficiency vastly superior to chemical engineering. As the chemical diversity of natural amino acids in proteins is limited, finding ways to include “unnatural” amino acids can supercharge biology with a range of new protein activities. While the genetic code can be expanded to make space for unnatural amino acids, the rarity of free codons and reliance on prokaryotic ....Genetic code expansion of a eukaryotic in vitro translation system. The genetic code programs biosynthesis of polypeptides with efficiency vastly superior to chemical engineering. As the chemical diversity of natural amino acids in proteins is limited, finding ways to include “unnatural” amino acids can supercharge biology with a range of new protein activities. While the genetic code can be expanded to make space for unnatural amino acids, the rarity of free codons and reliance on prokaryotic organisms limit the applicability of this approach. We will develop a new higher-organism cell-free protein production system that can incorporate multiple unnatural amino acids into defined points of proteins. This, enabling and broadly applicable technology, will be tested by constructing opioid biosensors.Read moreRead less
Molecular archaeology: new knowledge from molecular weight distributions of synthetic and natural polymers. This project will lead to new understanding of how natural and synthetic polymers are formed. Examples are the enzymatic processes that produce the subtle architecture of rice grains, and the processes that pose problems for developing new techniques for making novel polymer-based materials. The fundamental scientific knowledge from this project will provide a platform for the future devel ....Molecular archaeology: new knowledge from molecular weight distributions of synthetic and natural polymers. This project will lead to new understanding of how natural and synthetic polymers are formed. Examples are the enzymatic processes that produce the subtle architecture of rice grains, and the processes that pose problems for developing new techniques for making novel polymer-based materials. The fundamental scientific knowledge from this project will provide a platform for the future development of improved materials, and for superior grain varieties for food and industrial use. These advances will be of significant benefit to Australian industry and consumers.Read moreRead less
On-demand visible light degradable dental materials. This project aims to break new ground in the field of advanced adhesives by pioneering a unique system that can be cleaved with a defined visible light trigger, enabling the removal of previously bonded material without mechanical force. This would allow two materials to be strongly bonded, including dental crowns, braces and implants. The project will advance on-demand degradable materials design, introducing an advanced class of responsive n ....On-demand visible light degradable dental materials. This project aims to break new ground in the field of advanced adhesives by pioneering a unique system that can be cleaved with a defined visible light trigger, enabling the removal of previously bonded material without mechanical force. This would allow two materials to be strongly bonded, including dental crowns, braces and implants. The project will advance on-demand degradable materials design, introducing an advanced class of responsive networks for applications where reversible bonding is critical. It will have flow on benefits in future dental material applications and also have applications where simple-to-remove, temporary adhesives are required.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE140101553
Funder
Australian Research Council
Funding Amount
$395,220.00
Summary
A flexible virus-like particle delivery platform for next-generation vaccines. Murine polyomavirus (MPyV) capsid proteins self-assemble into spherical protein shells approximately 45 nm in diameter. Such virus-like particles (VLPs) are of considerable interest as bionanotechnological tools. The unique flexibility provided by MPyV VLPs will be exploited by exploring the ability of the interior cavity to retain bioactive cargos while engineering novel functionality on the exterior surface by 'mix- ....A flexible virus-like particle delivery platform for next-generation vaccines. Murine polyomavirus (MPyV) capsid proteins self-assemble into spherical protein shells approximately 45 nm in diameter. Such virus-like particles (VLPs) are of considerable interest as bionanotechnological tools. The unique flexibility provided by MPyV VLPs will be exploited by exploring the ability of the interior cavity to retain bioactive cargos while engineering novel functionality on the exterior surface by 'mix-and-match' assembly of VLPs from modified components. As a proof of concept for next-generation vaccines that stimulate much needed, broadly protective responses against infectious diseases, model antigens will be delivered to specific immune cells using this nano-container.Read moreRead less
Developing orthogonal synthetic signaling cascades. This project proposes a generic approach for the construction of molecular switches based on artificially autoinhibited proteases. The bottom-up design of protein-based signaling networks is a key goal of synthetic biology. Yet, this remains elusive due to our inability to tailor-make signal transducers and receptors that can be readily compiled into defined signaling networks. Using structure-guided design and directed protein evolution, a set ....Developing orthogonal synthetic signaling cascades. This project proposes a generic approach for the construction of molecular switches based on artificially autoinhibited proteases. The bottom-up design of protein-based signaling networks is a key goal of synthetic biology. Yet, this remains elusive due to our inability to tailor-make signal transducers and receptors that can be readily compiled into defined signaling networks. Using structure-guided design and directed protein evolution, a set of protease-based signal transducers and ligand activated allosteric receptors will be created. The developed components are intended to be used to construct artificial signaling networks in mammalian cells that are orthogonal to the endogenous signaling cascades.Read moreRead less
From trash to treasure: engineering waste carbon utilisation in yeast. This project aims to engineer yeast to convert carbon dioxide- and methane-derived methanol into sustainable chemicals, foods, and pharmaceuticals. This project expects to generate new design principles for methanol metabolism by using the innovative approach of laboratory evolution along with state-of-the-art bio-engineering capabilities at Macquarie University and The University of Queensland. Expected outcomes of this proj ....From trash to treasure: engineering waste carbon utilisation in yeast. This project aims to engineer yeast to convert carbon dioxide- and methane-derived methanol into sustainable chemicals, foods, and pharmaceuticals. This project expects to generate new design principles for methanol metabolism by using the innovative approach of laboratory evolution along with state-of-the-art bio-engineering capabilities at Macquarie University and The University of Queensland. Expected outcomes of this project include new manufacturing processes for chemicals and foods, discovery of novel metabolism in yeast, and enhanced collaboration between Australia, Denmark, and the United States. This Project will provide benefits through sustainable bio-manufacturing, new economic activity, and reduced greenhouse gas emissions.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