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
Combining new synthetic biology tools to boost crop CO2 capture and growth. A solution for improving crop yield is to enhance the carbon dioxide fixation properties of the enzyme Rubisco whose inefficient activity often limits plant growth. This project makes use of new synthetic biology capabilities to artificially evolve Rubisco in the laboratory and select for new versions with improved performance. These beneficial changes will be introduced into crop Rubisco using targeted gene editing appr ....Combining new synthetic biology tools to boost crop CO2 capture and growth. A solution for improving crop yield is to enhance the carbon dioxide fixation properties of the enzyme Rubisco whose inefficient activity often limits plant growth. This project makes use of new synthetic biology capabilities to artificially evolve Rubisco in the laboratory and select for new versions with improved performance. These beneficial changes will be introduced into crop Rubisco using targeted gene editing approaches and the improvements in photosynthesis, growth and yield evaluated. This information will aid complimentary biotechnological efforts seeking to supercharge photosynthesis and help deliver the second Green Revolution needed to meet the improvement required in future agriculture productivity and resource use.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
Protein biosensors for detecting smoke exposure of grapes. Bush fires and controlled burns that take place in the vicinity of vineyards can lead to grape contamination with tasteless phenolic glucosides. Their hydrolysis during wine making leads to “smoke taint” – an unpleasant medicinal taste that can render wine undrinkable. We will apply a combination of organic synthesis, protein engineering and directed evolution to develop protein-based biosensors of phenolic glucosides. These biosensors w ....Protein biosensors for detecting smoke exposure of grapes. Bush fires and controlled burns that take place in the vicinity of vineyards can lead to grape contamination with tasteless phenolic glucosides. Their hydrolysis during wine making leads to “smoke taint” – an unpleasant medicinal taste that can render wine undrinkable. We will apply a combination of organic synthesis, protein engineering and directed evolution to develop protein-based biosensors of phenolic glucosides. These biosensors will be used to devise a simple portable colorimetric test that can be performed in the vineyard or the winery. The ability to rapidly determine the level of grape contamination with phenolic glucosides would give Australian wine growers and wine makers a powerful tool to mitigate the effects of bushfires.Read moreRead less
A new platform technology for gene therapy . The project aims to make a landmark contribution to biological science by enabling programmed delivery of therapeutic payloads from biocompatible materials. It will employ a novel synthetic biology approach to form two distinct peptide-enabled molecular architectures in a single system. This is expected to deliver a platform technology that will allow successful programmed delivery of viral vectors. The project is likely to deliver significant societa ....A new platform technology for gene therapy . The project aims to make a landmark contribution to biological science by enabling programmed delivery of therapeutic payloads from biocompatible materials. It will employ a novel synthetic biology approach to form two distinct peptide-enabled molecular architectures in a single system. This is expected to deliver a platform technology that will allow successful programmed delivery of viral vectors. The project is likely to deliver significant societal benefit as a fundamental scientific platform, improving Australia's capacity and impact in the agriculture and the healthcare sectors. The platform technology has the potential to increase the quality of life for patients and their carers, while also produce fitter, healthier livestock.Read moreRead less
In vitro expression of macrocyclic peptides. This project aims to develop a novel strategy for the production of polypeptides with unnatural chemical groups using a sense codon reassignment approach. Novel peptides could be used in a range of pharmaceutical applications. Peptides made of 20 natural amino acids cover only a very small fraction of the available chemical and functional space. While a peptide’s functionality can be extended with unnatural amino acids, the methods for their site-sele ....In vitro expression of macrocyclic peptides. This project aims to develop a novel strategy for the production of polypeptides with unnatural chemical groups using a sense codon reassignment approach. Novel peptides could be used in a range of pharmaceutical applications. Peptides made of 20 natural amino acids cover only a very small fraction of the available chemical and functional space. While a peptide’s functionality can be extended with unnatural amino acids, the methods for their site-selective incorporation are inefficient. The project’s strategy relies on the depletion of selected tRNAs from an in vitro protein translation system and their replacement with synthetic tRNAs, charged with unnatural amino acids. It is expected that the developed technology could be used to rapidly generate and screen highly diversified macrocyclic peptide libraries.Read moreRead less
Light-driven biocatalytic cell factories. This project aims to develop single-cell algae optimised for high-efficiency green hydrogen production from cheap, sustainable resources - sunlight and water. The success of this project would be a game changer for industry by dramatically improving light to fuel conversion efficiencies. The expected high-efficiency cells would be a valuable resource for a wide range of other light-driven advanced bio-manufacture applications from high-value biopharmaceu ....Light-driven biocatalytic cell factories. This project aims to develop single-cell algae optimised for high-efficiency green hydrogen production from cheap, sustainable resources - sunlight and water. The success of this project would be a game changer for industry by dramatically improving light to fuel conversion efficiencies. The expected high-efficiency cells would be a valuable resource for a wide range of other light-driven advanced bio-manufacture applications from high-value biopharmaceuticals (e.g. <10 Hectare scale) through to renewable fuels (e.g. 10-1000 Hectare regional scale). The benefits would include advanced green chemical and biochemical manufacturing, diversified sources for green H2 production, regional development, industry growth, job security and exports.Read moreRead less
Ancestral enzyme engineering for designer fat products. Consumers are increasingly turning to plant-based alternatives of meat and dairy products due to concerns about health, animal welfare and sustainability. Taste, nutritional profile, protein content and limited variety are barriers that continue to challenge food manufacturers. This project aims to develop a process for the fermentation of specialty food oils and fats from agriculture production waste, that can deliver the flavour and nutri ....Ancestral enzyme engineering for designer fat products. Consumers are increasingly turning to plant-based alternatives of meat and dairy products due to concerns about health, animal welfare and sustainability. Taste, nutritional profile, protein content and limited variety are barriers that continue to challenge food manufacturers. This project aims to develop a process for the fermentation of specialty food oils and fats from agriculture production waste, that can deliver the flavour and nutritional benefits of meat and dairy products when added to plant-based alternatives. The outcomes should valorise existing agriculture and food waste, converting waste materials into valuable food ingredients.Read moreRead less