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A genomic and phenomic investigation of a mitochondrial glutathione transferase. The aim of this study is to understand of the genomics, structure and function of glutathione transferase Kappa (GSTK), a novel GST found in mitochondria. The investigations will achieve several outcomes. (1)an understanding of the organisation of GSTK gene(s) in humans and mice; (2) determination of the role of GSTK in mitochondria, by investigating the phenotype of knockout mice; (3) determination of the crysta ....A genomic and phenomic investigation of a mitochondrial glutathione transferase. The aim of this study is to understand of the genomics, structure and function of glutathione transferase Kappa (GSTK), a novel GST found in mitochondria. The investigations will achieve several outcomes. (1)an understanding of the organisation of GSTK gene(s) in humans and mice; (2) determination of the role of GSTK in mitochondria, by investigating the phenotype of knockout mice; (3) determination of the crystal structure of human GSTK; (4) An understanding of GSTK's substrate specificity, reaction kinetics and structure/function relationships. Since GSTK is confined to mitochondria, and may not be related to other GSTs, we may also identify novel functionsRead moreRead less
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
An investigation into flagellotropic bacteriophage stability and biology. This project aims to understand the capabilities of a type of virus called bacteriophage (phage). Significant economic loss in the food industry has led the USA and Europe to deploy phage to decontaminate food-processing machinery. These phage kill food-spoiling bacteria. This project expects to fill gaps in our knowledge, particularly to assit in choosing phage that are of increased stability and thus more long-lasting fo ....An investigation into flagellotropic bacteriophage stability and biology. This project aims to understand the capabilities of a type of virus called bacteriophage (phage). Significant economic loss in the food industry has led the USA and Europe to deploy phage to decontaminate food-processing machinery. These phage kill food-spoiling bacteria. This project expects to fill gaps in our knowledge, particularly to assit in choosing phage that are of increased stability and thus more long-lasting for deployment in industrial settings, and to inform additives to the phage preparations to increase their potency in killing bacteria. The project should provide significant benefits in training students and staff in methodology for investigating phage for future applications in Australian industry and biotechnology.
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Identifying genes controlling the regulatory and metabolic interactions between the energy organelles of the leaf. Plant energy metabolism underlies the synthesis of many important products in crops, and subtle changes in metabolism can enhance key plant traits, such as germination rates, early seedling vigour, biomass/yield, and tolerance to harsh environments. Furthering our understanding on the complex interplay of genes controlling energy metabolism and its impact on leaf function has potent ....Identifying genes controlling the regulatory and metabolic interactions between the energy organelles of the leaf. Plant energy metabolism underlies the synthesis of many important products in crops, and subtle changes in metabolism can enhance key plant traits, such as germination rates, early seedling vigour, biomass/yield, and tolerance to harsh environments. Furthering our understanding on the complex interplay of genes controlling energy metabolism and its impact on leaf function has potential outcomes for smart genetic manipulation either by classical breeding or genetic transformation. There are more than 10,000 genes of unknown function in plant genomes and this represents a tremendous untapped resource for future Australian R&D outcomes and insights from this research proposal will have application to all plant-based agriculture.Read moreRead less
Australian Laureate Fellowships - Grant ID: FL160100170
Funder
Australian Research Council
Funding Amount
$2,887,531.00
Summary
Scaling in biology: size control at the cell, organelle and organism level. This project aims to decipher the universal mechanisms that coordinate growth with division and thereby dictate the size of the cell. It would investigate this question from the triangulating perspective of evolution using yeast and animal models. It plans to interrogate the complex sub-networks that govern cell size using novel genome-scale reagent sets for systematic genetics and other approaches. It would integrate th ....Scaling in biology: size control at the cell, organelle and organism level. This project aims to decipher the universal mechanisms that coordinate growth with division and thereby dictate the size of the cell. It would investigate this question from the triangulating perspective of evolution using yeast and animal models. It plans to interrogate the complex sub-networks that govern cell size using novel genome-scale reagent sets for systematic genetics and other approaches. It would integrate this data in predictive mathematical models of size control that illuminate how the cell processes size-related information, and how size mechanisms evolve to impact form and function in biology. This research is expected to have commercial applications in biotechnology processes and bioengineering.Read moreRead less
Cystine flux and hydrogen peroxide breakdown in reuteri group lactobacilli. We have discovered, and aim to fully dissect a novel function of reuteri group lactobacilli. These microbes inhabit the surfaces of the gastrointestinal and reproductive tracts of humans and are also used as probiotics, and in the dairy industry. This function mediates the production and breakdown of large amounts of hydrogen peroxide, cystine and thiols. These are highly bioactive and affect human cells and other bacter ....Cystine flux and hydrogen peroxide breakdown in reuteri group lactobacilli. We have discovered, and aim to fully dissect a novel function of reuteri group lactobacilli. These microbes inhabit the surfaces of the gastrointestinal and reproductive tracts of humans and are also used as probiotics, and in the dairy industry. This function mediates the production and breakdown of large amounts of hydrogen peroxide, cystine and thiols. These are highly bioactive and affect human cells and other bacteria at the surfaces of the gastrointestinal and reproductive tracts, and thiols are also flavourants in dairy products. Our research will inform the rational development of probiotics, the management and treatment of unpleasant conditions such as Crohn's disease and bacterial vaginosis, and innovation in dairy fermentations.Read moreRead less
Blood component interactions with polysaccharide biomaterials for vascular applications. Heart disease is the major killer of people in Australia and the Western world. It is due mainly to the blockage of vessels supplying the muscle of the heart with blood and nutrients, which can be replaced or by-passed but the supply of native vessels in the body is limited. Tissue engineering laboratories have been trying to develop blood vessels for this use for many years without significant success. T ....Blood component interactions with polysaccharide biomaterials for vascular applications. Heart disease is the major killer of people in Australia and the Western world. It is due mainly to the blockage of vessels supplying the muscle of the heart with blood and nutrients, which can be replaced or by-passed but the supply of native vessels in the body is limited. Tissue engineering laboratories have been trying to develop blood vessels for this use for many years without significant success. This application plans to understand the molecular signals contained within the sugar sequences used in a commonly used biomaterial chitosan that may be used in the construction of synthetic vascular grafts. If we can understand how blood cells interact with this biomaterial, we may be able to develop a blood vessel in the laboratory.Read moreRead less
Nucleotides for bioelectronics. Bioelectronics is a key component of nanobiotechnology, a new field that merges the science of biological molecules (DNA, proteins etc.) with electronics and semiconductor physics. We have recently introduced redox-labelled nucleotides that enable the production of electrochemically-active DNA and RNA for genetic, forensic and nanotechnology applications. This project further develops redox nucleotides for use in electronic devices.
Three-dimensional structures, substrate specificities and catalytic mechanisms of polysaccharide synthases. Plant wall polysaccharides are extensively used for food and fibre, and are important dietary components in human nutrition. A precise knowledge of mechanisms used by plants to synthesize these polysaccharides is unavailable, but would reveal potential routes to manipulate their biosynthesis in important crop species. For example, the levels or structures of polysaccharides might be modif ....Three-dimensional structures, substrate specificities and catalytic mechanisms of polysaccharide synthases. Plant wall polysaccharides are extensively used for food and fibre, and are important dietary components in human nutrition. A precise knowledge of mechanisms used by plants to synthesize these polysaccharides is unavailable, but would reveal potential routes to manipulate their biosynthesis in important crop species. For example, the levels or structures of polysaccharides might be modified to improve their efficacy as anti-cancer agents in human diets, to enhance digestibility of animal stock feeds, or to synthesise pharmologically valuable compounds. Thus, economic, social and environmental benefits will flow to both producers and consumers. Read moreRead less