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Investigation of a Novel Protein Implicated in Phosphate Metabolism in Bacteria. Phosphate is an important nutrient for all forms of life on Earth. A novel bacterial protein has been identified that appears to be important for the uptake or processing of phosphate, since mutants lacking the protein grow poorly inside certain cells of the human immune system (where phosphate levels are low) and in media containing low phosphate. The aims of this project are: to determine the role of the protein b ....Investigation of a Novel Protein Implicated in Phosphate Metabolism in Bacteria. Phosphate is an important nutrient for all forms of life on Earth. A novel bacterial protein has been identified that appears to be important for the uptake or processing of phosphate, since mutants lacking the protein grow poorly inside certain cells of the human immune system (where phosphate levels are low) and in media containing low phosphate. The aims of this project are: to determine the role of the protein by examining all phosphate containing molecules in our mutants; to determine its location in bacteria and functional domains; to identify other affected genes in our mutants; and, to find proteins that interact with this new protein. This project expects to demonstrate the importance of this protein in phosphate metabolism in bacteria.Read moreRead less
Augmenting the activity of glyoxalase-1 to increase dicarbonyl clearance . Reactive intermediates generated during our metabolism contribute to ageing. Glyoxalase-1 is a key defence enzyme against these toxic intermediates and therefore ageing itself. This project aims to investigate novel pathways how the expression and activity of glyoxalase-1 are regulated. This interdisciplinary project expects to generate new understanding by combining relevant cell and animal models, protein chemistry, epi ....Augmenting the activity of glyoxalase-1 to increase dicarbonyl clearance . Reactive intermediates generated during our metabolism contribute to ageing. Glyoxalase-1 is a key defence enzyme against these toxic intermediates and therefore ageing itself. This project aims to investigate novel pathways how the expression and activity of glyoxalase-1 are regulated. This interdisciplinary project expects to generate new understanding by combining relevant cell and animal models, protein chemistry, epigenetics and structural biology. It is expected that this work will improve understanding of this fundamental biological defence. This will allow us to identify the potential means to enhance the capacity of glyoxalase-1 to the future benefit of biological ageing.Read moreRead less
Structure and Function of the AMP-activated protein kinase. The AMP-activated protein kinase (AMPK) is a member of the metabolic stress sensing protein kinase subfamily that is present in all eukaryotes, including the yeast homologue, snf1p protein kinase essential for adapting to growth without glucose. The AMPK plays an important role in matching metabolism to nutrient supply and energy demand of perhaps all physiological processes. The aim of this project is to understand the structure and ....Structure and Function of the AMP-activated protein kinase. The AMP-activated protein kinase (AMPK) is a member of the metabolic stress sensing protein kinase subfamily that is present in all eukaryotes, including the yeast homologue, snf1p protein kinase essential for adapting to growth without glucose. The AMPK plays an important role in matching metabolism to nutrient supply and energy demand of perhaps all physiological processes. The aim of this project is to understand the structure and function of the AMPK. This work may provide important opportunities for drug design, understanding the impact of metabolism and ageing as well as increasing our knowledge of signalling pathways that control cellular events.Read moreRead less
Coordinating energy metabolism to enhance exercise capacity. Diet and exercise contribute to health and ageing productively whereas high caloric diets and sedentary life styles are deleterious. The enzyme AMPK regulates energy metabolism in response to diet and exercise and by studying it we expect to learn why diet and exercise are beneficial at the molecular level. This may allow the development of nutritional, exercise and drug strategies to enhance exercise capacity and well being during ....Coordinating energy metabolism to enhance exercise capacity. Diet and exercise contribute to health and ageing productively whereas high caloric diets and sedentary life styles are deleterious. The enzyme AMPK regulates energy metabolism in response to diet and exercise and by studying it we expect to learn why diet and exercise are beneficial at the molecular level. This may allow the development of nutritional, exercise and drug strategies to enhance exercise capacity and well being during ageing as well as suppress age onset diseases that include obesity diabetes cardiovascular disease hypertension and neurodegeneration.Read moreRead less
Systems therapeutics for metabolism: AMPK isoform specific drugs. Living cells have to maintain a steady balance between energy production and consumption in order to function properly. A key regulator of energy balance is an enzyme known as 5' AMP-activated protein kinase (AMPK), which regulates the burning and storage of fuels such as fat and sugars, in response to changes in energy demand. This project will provide a major advancement in our understanding of the regulation of AMPK at the mo ....Systems therapeutics for metabolism: AMPK isoform specific drugs. Living cells have to maintain a steady balance between energy production and consumption in order to function properly. A key regulator of energy balance is an enzyme known as 5' AMP-activated protein kinase (AMPK), which regulates the burning and storage of fuels such as fat and sugars, in response to changes in energy demand. This project will provide a major advancement in our understanding of the regulation of AMPK at the molecular level, and lay the foundations for the development of more effective drugs to treat energy balance disorders such as obesity and Type 2 diabetes. Furthermore, this proposal will contribute to enriching Australia's international profile and competitiveness in this important area of research.Read moreRead less
Mechanism of AMPK activation by drugs and metabolites. This project aims to identify the molecular basis of activation mechanisms in the AMP-activated protein kinase (AMPK), an enzyme that regulates burning and storage of fuels such as fat and sugars, autophagy and controls appetite and energy expenditure. This project expects to provide insights into how energy metabolism and physiological functions are linked.
New models of mitochondrial fatty acid oxidation disorders. Mitochondrial disease can affect both children and adults and is often fatal. This project will study mitochondrial function in cell types of the heart and brain to better understand how they generate energy in these tissues. This will provide new insights into mitochondrial metabolism and how defects in this process cause mitochondrial disease.