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
Striving for the path of least herbicide resistance. This project aims to investigate novel strategies to mitigate the rise in herbicide resistance threatening Australian agricultural production and exports. The project expects to pioneer long-term strategies for the development of herbicides that “resist” resistance generation in weeds to prolong their effectiveness. Expected outcomes include advances in the development of single- and multi-target herbicidal compounds with new modes of action, ....Striving for the path of least herbicide resistance. This project aims to investigate novel strategies to mitigate the rise in herbicide resistance threatening Australian agricultural production and exports. The project expects to pioneer long-term strategies for the development of herbicides that “resist” resistance generation in weeds to prolong their effectiveness. Expected outcomes include advances in the development of single- and multi-target herbicidal compounds with new modes of action, and validation of their potential to yield synergistic combinations and delay the evolution of resistance. This should lay the foundations for significant long-term benefits to farmers and consumers, both in Australia and globally, including increased crop yields and improved food security.Read moreRead less
Regulation of autophagy dependent cell and tissue deletion. This project aims to elucidate novel mechanisms that regulate autophagy-depdendent cell death during animal development. It will combine the power of Drosophila genetics with multidisciplinary approaches, such as proteomics, bioinformatics and cell biology. Given the conserved nature of autophagy the oucomes will provide highly topical and exciting new knowledge of broad biological significance. The project will help establishing inter ....Regulation of autophagy dependent cell and tissue deletion. This project aims to elucidate novel mechanisms that regulate autophagy-depdendent cell death during animal development. It will combine the power of Drosophila genetics with multidisciplinary approaches, such as proteomics, bioinformatics and cell biology. Given the conserved nature of autophagy the oucomes will provide highly topical and exciting new knowledge of broad biological significance. The project will help establishing international collaborations, enhancing Australia’s competitiveness and reputation in an important area of research, and provide training of HDR students in skills across a range of areas. In the long-term the research findings may translate into improved agriculture, food production and human health outcomes.Read moreRead less
The LINK to Regulating Lysine Levels in Wheat. This project aims to characterise a recently discovered allosteric mechanism called 'Ligand-Induced association by Lysine (K)' (LINK) model. LINK model regulates the function of a key biosynthetic enzyme in bacteria and plants, including agriculturally-important species such as wheat. Also, it represents a highly significant discovery to the field of biochemistry. The expected outcomes of this project include an in-depth understanding of the molecul ....The LINK to Regulating Lysine Levels in Wheat. This project aims to characterise a recently discovered allosteric mechanism called 'Ligand-Induced association by Lysine (K)' (LINK) model. LINK model regulates the function of a key biosynthetic enzyme in bacteria and plants, including agriculturally-important species such as wheat. Also, it represents a highly significant discovery to the field of biochemistry. The expected outcomes of this project include an in-depth understanding of the molecular basis of a new allosteric mechanism for regulating intracellular lysine levels, which in the longer term offers excellent potential to be manipulated for agricultural benefits.Read moreRead less
Alternative Oxidase to Optimise Plant Growth and Stress Tolerance. Biomass accumulation in plants is the balance of CO2 fixed into carbohydrates through photosynthesis and carbohydrate burned (respired), ~ 50% of fixed CO2, to fuel growth. Plants possess energy conserving and non-conserving respiratory pathways. The alternative energy non-conserving pathway appears wasteful but is necessary for plant tolerance to adverse growth conditions. Our research has achieved modification of the alternativ ....Alternative Oxidase to Optimise Plant Growth and Stress Tolerance. Biomass accumulation in plants is the balance of CO2 fixed into carbohydrates through photosynthesis and carbohydrate burned (respired), ~ 50% of fixed CO2, to fuel growth. Plants possess energy conserving and non-conserving respiratory pathways. The alternative energy non-conserving pathway appears wasteful but is necessary for plant tolerance to adverse growth conditions. Our research has achieved modification of the alternative respiratory pathway that positively impacts plant growth. We will dissect the mechanism(s) of how the alternative respiratory pathway stimulates growth, from a molecular level to whole plant physiology, answering a long-standing question of the role of the alternative respiratory pathway in plant cell biology.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE190100806
Funder
Australian Research Council
Funding Amount
$419,854.00
Summary
Towards herbicide cocktails with a new mode of action to avert resistance. This project aims to target herbicide resistant weeds which represent one of the largest threats to Australian and global food security. Targeting of unexplored pathways in plants to develop a novel herbicide strategy is expected to be achieved, and will include the structural and functional characterisation of key enzymes in these pathways. This project is expected to provide significant benefits for effective weed manag ....Towards herbicide cocktails with a new mode of action to avert resistance. This project aims to target herbicide resistant weeds which represent one of the largest threats to Australian and global food security. Targeting of unexplored pathways in plants to develop a novel herbicide strategy is expected to be achieved, and will include the structural and functional characterisation of key enzymes in these pathways. This project is expected to provide significant benefits for effective weed management to sustain Australia’s agricultural industry through enhanced food production from increased crop yields, whilst ensuring food security. These outcomes, coupled with decades of over-reliance on current herbicides, means there has never been a greater need for new and effective herbicides.Read moreRead less
The design of targetable epigenetic modifiers. The project aims to engineer enzymes as valuable tools for understanding gene expression mechanisms and potentially a technology for altering gene expression in plants, animals or humans in a targetable manner. The genetic information encoded in the DNA of all complex organisms has been shown to be augmented by decorations on both DNA and the histone proteins that package DNA. This so-called epigenetic information is important but not well understoo ....The design of targetable epigenetic modifiers. The project aims to engineer enzymes as valuable tools for understanding gene expression mechanisms and potentially a technology for altering gene expression in plants, animals or humans in a targetable manner. The genetic information encoded in the DNA of all complex organisms has been shown to be augmented by decorations on both DNA and the histone proteins that package DNA. This so-called epigenetic information is important but not well understood. The project plans to design highly specific and targetable enzymes that can interrogate and manipulate epigenetic information in living cells. Understanding the regulation of gene expression and controlling the expression of chosen genes may form a foundation for applications in agriculture, biology and medicine.Read moreRead less
Functional evolution and therapeutic potential of snake venom coagulotoxins. This project aims to identify and understand the factors that influence the useful function of key residues (parts of larger compounds) in Australian snake venom coagulotoxins, which alter blood-clotting ability. In recent years, snake venom compounds have been demonstrated as useful models from which to synthesise therapeutic drugs to improve health and well-being. This project will test these important toxins on model ....Functional evolution and therapeutic potential of snake venom coagulotoxins. This project aims to identify and understand the factors that influence the useful function of key residues (parts of larger compounds) in Australian snake venom coagulotoxins, which alter blood-clotting ability. In recent years, snake venom compounds have been demonstrated as useful models from which to synthesise therapeutic drugs to improve health and well-being. This project will test these important toxins on model systems that represent natural prey items in order to determine the molecular and functional evolution of blood-clot forming enzymes. Expected outcomes include substantial contributions to the body of evolutionary biology knowledge, as well as narrowing the search for the ultimate drug candidates.Read moreRead less
Modulation of cellular metabolism by protein and peptide peroxides. Oxidation of peptides and proteins by a wide range of reactive radicals and other oxidants, in the presence of oxygen, generates protein peroxides. These species are now recognised to be key intermediates in both the deterioration of foods (e.g. development of rancidity and off-flavours, changes in colour and texture) and a number of human diseases, including cancer, heart disease and ageing. How these peroxides cause biological ....Modulation of cellular metabolism by protein and peptide peroxides. Oxidation of peptides and proteins by a wide range of reactive radicals and other oxidants, in the presence of oxygen, generates protein peroxides. These species are now recognised to be key intermediates in both the deterioration of foods (e.g. development of rancidity and off-flavours, changes in colour and texture) and a number of human diseases, including cancer, heart disease and ageing. How these peroxides cause biological perturbations is poorly understood. The proposed studies will provide valuable information as to how these peroxides affect cellular metabolism and provide key leads as to strategies which may prevent such damage.Read moreRead less
Mechanistic studies on the oxidation of amino acids, peptides and proteins and its biological consequences. Exposure of amino acids and proteins to radicals, oxidants, UV light, and metal ions results in oxidation, with consequent alteration to protein structure and function. It has been shown that these reactions occur during food spoilage, exposure of plants to excess UV light, and in a number of human diseases (e.g. heart disease and cancer). Despite evidence for a key role for protein oxidat ....Mechanistic studies on the oxidation of amino acids, peptides and proteins and its biological consequences. Exposure of amino acids and proteins to radicals, oxidants, UV light, and metal ions results in oxidation, with consequent alteration to protein structure and function. It has been shown that these reactions occur during food spoilage, exposure of plants to excess UV light, and in a number of human diseases (e.g. heart disease and cancer). Despite evidence for a key role for protein oxidation in these events, the fundamental chemistry and biochemistry of protein oxidation is incompletely understood. This is addressed in this project. Knowledge of the mechanisms of these reactions is a vital pre-requisite to the rational design of preventative strategies that might enhance food quality, minimise UV damage and enhance human health.Read moreRead less