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 and synthesis of angiotensin converting enzyme-2 (ACE2) inhibitors. A vast number of current drugs on the market are inhibitors of enzymes whose action needs to be controlled in order to treat many conditions. This proposal will apply our new approaches to the design of enzyme inhibitors with superior therapeutic action. The benefits of this research reside in new treatments for a range of cardiovascular diseases (the 3rd largest cause of mortality in Australia) and provide a platform ....The design and synthesis of angiotensin converting enzyme-2 (ACE2) inhibitors. A vast number of current drugs on the market are inhibitors of enzymes whose action needs to be controlled in order to treat many conditions. This proposal will apply our new approaches to the design of enzyme inhibitors with superior therapeutic action. The benefits of this research reside in new treatments for a range of cardiovascular diseases (the 3rd largest cause of mortality in Australia) and provide a platform for new biotech companies to be formed in Australia.Read moreRead less
Structural studies of mammalian dimeric dihydrodiol dehydrogenase and L-xylulose reductase. The aim of the research is determine the structures and mechanisms of mammalian dimeric dihrodiol dehydrogenase and L-xylulose reductase. Mammalian dihydrodiol dehydrogenase exists in multiple forms in mammalian tissues. The dimeric form of the enzyme has a primary structure distinct from previously known mammalian enzymes and may constitute a novel protein family with prokaryotic proteins. L-Xylulose ....Structural studies of mammalian dimeric dihydrodiol dehydrogenase and L-xylulose reductase. The aim of the research is determine the structures and mechanisms of mammalian dimeric dihrodiol dehydrogenase and L-xylulose reductase. Mammalian dihydrodiol dehydrogenase exists in multiple forms in mammalian tissues. The dimeric form of the enzyme has a primary structure distinct from previously known mammalian enzymes and may constitute a novel protein family with prokaryotic proteins. L-Xylulose reductase is an enzyme of the uronate cycle that accounts for about 5% of the total glucose metabolism per day in humans. We propose to determine the first structure of a L-xylulose reductase.Read moreRead less
Special Research Initiatives - Grant ID: SR0354892
Funder
Australian Research Council
Funding Amount
$40,000.00
Summary
The Australian Protease Network. Proteases are pivotal enzymes during birth, life, ageing and death of all organisms. Proteases regulate most physiological processes by controlling protein activation, synthesis and turnover and are essential for replication and spread of viruses, bacteria and parasites that cause infectious diseases. Blockbuster drugs and diagnostics already target a few proteases. Australians have made innovative contributions individually to understanding and regulating these ....The Australian Protease Network. Proteases are pivotal enzymes during birth, life, ageing and death of all organisms. Proteases regulate most physiological processes by controlling protein activation, synthesis and turnover and are essential for replication and spread of viruses, bacteria and parasites that cause infectious diseases. Blockbuster drugs and diagnostics already target a few proteases. Australians have made innovative contributions individually to understanding and regulating these enzymes. However this initiative aims to network their efforts by value-adding to the current protease research through promoting national and international collaborations to improve our understanding of biology, and encourage exploitation of proteases/inhibitors/receptors for pharmaceutical and industrial applications.Read moreRead less
Studies on the stereospecific interaction between aldose reductase and inhibitor. There is no therapy specific for treatment of diabetes complications accepted worldwide. The enzyme aldose reductase has shown promising results as a drug target for preventing or delaying the onset of the complications. The structures of human aldose reductase holoenzyme in complex with stereoisomers of the potent inhibitor Fidarestat will be determined at high resolution in order to elucidate the binding modes re ....Studies on the stereospecific interaction between aldose reductase and inhibitor. There is no therapy specific for treatment of diabetes complications accepted worldwide. The enzyme aldose reductase has shown promising results as a drug target for preventing or delaying the onset of the complications. The structures of human aldose reductase holoenzyme in complex with stereoisomers of the potent inhibitor Fidarestat will be determined at high resolution in order to elucidate the binding modes responsible for the differences in their inhibitory potencies. The results may lead to the design of better inhibitors of the enzyme for the treatment of diabetes sufferers, at least until better methods for maintaining metabolic control are developed.Read moreRead less
Structure-based discovery of dipeptidyl peptidase IV inhibitors. Diabetes afflicts approximately 151 million people worldwide, with an estimated increase to 221 million by 2010. To date, no therapy for the treatment of diabetes complications is widely accepted. The enzyme dipeptidyl peptidase IV has shown promising results as a target for the treatment of type 2 diabetes. Structural studies of dipeptidyl peptidase IV in complex with inhibitor will be conducted to elucidate the details of the e ....Structure-based discovery of dipeptidyl peptidase IV inhibitors. Diabetes afflicts approximately 151 million people worldwide, with an estimated increase to 221 million by 2010. To date, no therapy for the treatment of diabetes complications is widely accepted. The enzyme dipeptidyl peptidase IV has shown promising results as a target for the treatment of type 2 diabetes. Structural studies of dipeptidyl peptidase IV in complex with inhibitor will be conducted to elucidate the details of the enzyme-inhibitor interaction. The results will be used to identify the molecular basis of potency and selectivity of dipeptidyl peptidase IV inhibitors and may lead to the discovery of pharmaceutical agents for the treatment of diabetes sufferers.Read moreRead less
Crystallographic studies of aldose and aldehyde reductases. The ability of aldose reductase to reduce the excess glucose that results from the hyperglycaemia of diabetes has been linked to the development of diabetic complications. Recent studies link the lack of a clinically suitable aldose reductase inhibitor to lack of inhibitor selectivity. The structures of the complexes of aldose and aldehyde reductases with various inhibitors should allow us to establish the important aspects of the inh ....Crystallographic studies of aldose and aldehyde reductases. The ability of aldose reductase to reduce the excess glucose that results from the hyperglycaemia of diabetes has been linked to the development of diabetic complications. Recent studies link the lack of a clinically suitable aldose reductase inhibitor to lack of inhibitor selectivity. The structures of the complexes of aldose and aldehyde reductases with various inhibitors should allow us to establish the important aspects of the inhibitor interaction with the residues of the active site. This information will be used in the design of more specific aldose reductase inhibitors.Read moreRead less