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Molecular analysis of glutathione transferase interactions with drugs and physiological ligands. Proteins called glutathione transferases protect us from toxic molecules that we ingest, breathe in or are by-products of normal metabolism. The same proteins also bind to many types of drugs leading them to be excreted from the body. In this project molecular structures of glutathione transferases bound to anti-cancer drugs will be determined as the basis for devising inhibitors of the protein that ....Molecular analysis of glutathione transferase interactions with drugs and physiological ligands. Proteins called glutathione transferases protect us from toxic molecules that we ingest, breathe in or are by-products of normal metabolism. The same proteins also bind to many types of drugs leading them to be excreted from the body. In this project molecular structures of glutathione transferases bound to anti-cancer drugs will be determined as the basis for devising inhibitors of the protein that will make drugs much more effective.Read moreRead less
Structural studies of glutathione transferases: a model system for functional genomics and drug design. Glutathione S-transferases (GSTs) are a large family of multi-functional proteins that play a vital role in an organism's defence against toxic chemicals. However, they also attack a variety of drugs and hence are a prime target for the development of isoform-specific inhibitors. We will determine the 3D atomic structures of GSTs in complex with a range of substrates and inhibitors as a basis ....Structural studies of glutathione transferases: a model system for functional genomics and drug design. Glutathione S-transferases (GSTs) are a large family of multi-functional proteins that play a vital role in an organism's defence against toxic chemicals. However, they also attack a variety of drugs and hence are a prime target for the development of isoform-specific inhibitors. We will determine the 3D atomic structures of GSTs in complex with a range of substrates and inhibitors as a basis for the design of compounds to improve the efficacy of anti-cancer and other drugs. This is an ambitious, wide-ranging project involving collaborators around the world. We expect the results will not only greatly increase our knowledge of an important enzyme family, but will also have applications in protein folding, catalysis, protein engineering, evolution, drug design and functional genomics. Read moreRead less
Developing an integrated systems and synthetic biology platform to expand the product spectrum of acetogens. This project aims to advance a waste gas fermentation process to enable the production of sustainable aviation fuel molecules for the first time. LanzaTech are world leaders in microbial gas fermentation and have produced ethanol at large scale in China. This project aims to combine the LanzaTech process with systems biology expertise at The University of Queensland to go beyond ethanol t ....Developing an integrated systems and synthetic biology platform to expand the product spectrum of acetogens. This project aims to advance a waste gas fermentation process to enable the production of sustainable aviation fuel molecules for the first time. LanzaTech are world leaders in microbial gas fermentation and have produced ethanol at large scale in China. This project aims to combine the LanzaTech process with systems biology expertise at The University of Queensland to go beyond ethanol to deliver new value-added products such as butanediol and farnesene. To achieve this aim the project will explore, understand and overcome fundamental energy and metabolic limitations in the production microorganism. Achieving the aims will be of direct relevance to SkyNRG and the new Brisbane Bioport on their path to deliver sustainable fuel to Brisbane Airport.Read moreRead less
Toward sustainable diesel production using microbial cells: unravelling isoprenoid pathway regulation through systems biology. The methylerythritol pyrophosphate (MEP) pathway for isoprenoid production is an essential biochemical pathway. It was only fully elucidated a decade ago, and the regulatory controls over this pathway are not understood. The objective of this project is to elucidate the mechanisms by which the MEP pathway is controlled in E. coli using a novel systems biology approach. U ....Toward sustainable diesel production using microbial cells: unravelling isoprenoid pathway regulation through systems biology. The methylerythritol pyrophosphate (MEP) pathway for isoprenoid production is an essential biochemical pathway. It was only fully elucidated a decade ago, and the regulatory controls over this pathway are not understood. The objective of this project is to elucidate the mechanisms by which the MEP pathway is controlled in E. coli using a novel systems biology approach. Understanding control of the MEP pathway is required to gain insight into homeostatic control of this essential pathway, and enable biotechnological engineering of E. coli in order to produce a wide range of industrially useful isoprenoids (including biofuels, pharmaceuticals, industrial chemicals, neutraceuticals, food additives, perfumes and many more).Read moreRead less
Heterologous expression of cyanobacterial compounds of analytical and therapeutic value. The project team has previously discovered the genetic basis for toxin production in cyanobacteria and algae. This project aims to define the biochemical pathways of the unique biosynthetic enzymes involved in alkaloid and cyclic peptide toxin production in these microorganisms. Via the development of large-gene cloning strategies, the toxins will be produced in a stable, sustainable and secure fermentation ....Heterologous expression of cyanobacterial compounds of analytical and therapeutic value. The project team has previously discovered the genetic basis for toxin production in cyanobacteria and algae. This project aims to define the biochemical pathways of the unique biosynthetic enzymes involved in alkaloid and cyclic peptide toxin production in these microorganisms. Via the development of large-gene cloning strategies, the toxins will be produced in a stable, sustainable and secure fermentation system. These compounds will be critical for standardising toxin detection methods in water supplies globally and for assessing their bioactivities in humans and other animals. Research students and the industry partner will also be trained to apply these novel biotechnologies for the production of other drug-like molecules.Read moreRead less
Universal transcriptome editing technologies. Ribonucleic acid (RNA) is life’s most essential molecule – as no living cell or virus can function without it. Although RNA plays many critical roles in cells, from information transfer and regulation of gene expression to scaffolding macromolecular structures and catalysis, the current approaches to manipulate RNA for technological purposes are limited in many respects. This project brings together the scientists who were the first to discover a uni ....Universal transcriptome editing technologies. Ribonucleic acid (RNA) is life’s most essential molecule – as no living cell or virus can function without it. Although RNA plays many critical roles in cells, from information transfer and regulation of gene expression to scaffolding macromolecular structures and catalysis, the current approaches to manipulate RNA for technological purposes are limited in many respects. This project brings together the scientists who were the first to discover a universal code for recognition of RNA by proteins and one of the world’s leading RNA-focused biotechnology companies, Locana Biosciences, with the goal of providing robust and versatile tools to target RNA in diverse organisms.Read moreRead less
Non-classical steroid signalling through SF-1 responsive genes: a key mechanism in environmental endocrine disruption, cancer, and aging. Endocrine disruption by pervasive manmade chemicals, which mimic natural hormones, and are found in plastics, cosmetics, and fire retardants, is known to cause developmental defects in model organisms and wildlife, with substantial risk also to human health. This risk increases with increasing population density and dependence on water recycling. Current tests ....Non-classical steroid signalling through SF-1 responsive genes: a key mechanism in environmental endocrine disruption, cancer, and aging. Endocrine disruption by pervasive manmade chemicals, which mimic natural hormones, and are found in plastics, cosmetics, and fire retardants, is known to cause developmental defects in model organisms and wildlife, with substantial risk also to human health. This risk increases with increasing population density and dependence on water recycling. Current tests to assess such substances use oversimplified modes of hormone action and grossly underestimate the risk of endocrine disruption. This proposal will yield new knowledge about how such substances act in the body, or on wildlife, and form the basis for new more sensitive methods of environmental monitoring.Read moreRead less
Unleashing the Hidden Chemical Diversity in Australian Fungi. This project aims to exploit an exclusive genomic resource consisting of >150 unique Australian filamentous fungi that has been built in a university-industry collaboration for genomic-guided biodiscovery. The genome sequence of these fungi revealed extensive hidden genetic instructions for production of novel biologically active molecules. The project will apply cutting-edge synthetic biology and chemical tools to tap into the hidden ....Unleashing the Hidden Chemical Diversity in Australian Fungi. This project aims to exploit an exclusive genomic resource consisting of >150 unique Australian filamentous fungi that has been built in a university-industry collaboration for genomic-guided biodiscovery. The genome sequence of these fungi revealed extensive hidden genetic instructions for production of novel biologically active molecules. The project will apply cutting-edge synthetic biology and chemical tools to tap into the hidden genomic potential of these Australian fungi. Expected outcomes of this project include new fine chemicals and lead molecules with desirable bioactivies. This will provide significant benefits to Australia's economy through the discovery of new pharmaceuticals, veterinary products and agrichemicals.Read moreRead less
ARC Centre of Excellence in Synthetic Biology. The ARC Centre of Excellence in Synthetic Biology (CoESB) will provide the technical innovation critical for Australia to develop a vibrant bioeconomy building on the nation’s strengths in agriculture. For thousands of years we have used microbes to create bread, wine, cheese. Now, our Centre will pioneer new approaches to the design of synthetic microbes, enabling the development of custom-designed microbial communities, synthetic organelles and ne ....ARC Centre of Excellence in Synthetic Biology. The ARC Centre of Excellence in Synthetic Biology (CoESB) will provide the technical innovation critical for Australia to develop a vibrant bioeconomy building on the nation’s strengths in agriculture. For thousands of years we have used microbes to create bread, wine, cheese. Now, our Centre will pioneer new approaches to the design of synthetic microbes, enabling the development of custom-designed microbial communities, synthetic organelles and new to nature biological pathways and enzymes. CoESB will combine engineering with molecular biology to design and construct novel biological systems that can convert biomass from agriculture or waste streams to biofuel, bioplastics and other high-value chemicals.Read moreRead less
Nano-reactors: Protein cages as reusable scaffolds for designer enzymes. This project aims to develop robust protein cages derived from the coats of viruses to contain heat-stable P450 enzymes, for use as specialised protein bio-catalysts in chemical industries. A valuable chemical precursor of renewable bio-plastics will be produced from seed oils by enzymes, reducing the use of fossil fuels. This synthetic biology approach combines biotechnology, nanotechnology and protein engineering to estab ....Nano-reactors: Protein cages as reusable scaffolds for designer enzymes. This project aims to develop robust protein cages derived from the coats of viruses to contain heat-stable P450 enzymes, for use as specialised protein bio-catalysts in chemical industries. A valuable chemical precursor of renewable bio-plastics will be produced from seed oils by enzymes, reducing the use of fossil fuels. This synthetic biology approach combines biotechnology, nanotechnology and protein engineering to establish a plant-based platform biotechnology for using enzymes as catalysts to make high-value molecules. The project aims to show how to engineer clean, sustainable chemistry in designer nano-environments. This should make synthetic processes more sustainable and enhance advanced chemical manufacturing in Australia.Read moreRead less