Characterisation of molecular regulation of telomerase and telomeres by p53 in cell ageing. Telomeres, the ends of chromosomes shorten as a function of cell division, and thereby limit cell lifespan. Telomerase synthesizes telomeres and thus renders cells immortal. Recently, we found that p53, a protein with an important role in cell aging and in the uncontrolled growth of cancer, interacts with telomeres and telomerase by binding to the telomere proteins TRF1 and TRF2. This project will deciphe ....Characterisation of molecular regulation of telomerase and telomeres by p53 in cell ageing. Telomeres, the ends of chromosomes shorten as a function of cell division, and thereby limit cell lifespan. Telomerase synthesizes telomeres and thus renders cells immortal. Recently, we found that p53, a protein with an important role in cell aging and in the uncontrolled growth of cancer, interacts with telomeres and telomerase by binding to the telomere proteins TRF1 and TRF2. This project will decipher the mechanisms by which p53 regulates telomerase and telomeres, and establish the interrelationship of these proteins in regulating cell lifespan, death and immortalisation. It will provide important information for molecular intervention in cell ageing and immortalisation.Read moreRead less
Metals in biocatalysis. Metals and enzymes are essential for the chemistry of life. This project will aim to garner the potential of metal-dependent enzymes to develop new drugs against osteoporosis, combat the spread of antibiotics resistance and optimise some of these enzymes to detoxify pesticide-polluted environments, thus contributing to global health and food security.
Pathogenesis of Alzheimer's disease: Dissecting synaptosomal dysfunction in transgenic animal models. There is no cure for Alzheimer's disease (AD). This project will dissect pathogenic mechanisms, identify new drug targets, and develop treatment strategies, all of which will be patented and eventually lead to a decrease in health costs in Australia. This research clearly falls under the national research priority of promoting and maintaining good health. Our findings are expected to benefit pat ....Pathogenesis of Alzheimer's disease: Dissecting synaptosomal dysfunction in transgenic animal models. There is no cure for Alzheimer's disease (AD). This project will dissect pathogenic mechanisms, identify new drug targets, and develop treatment strategies, all of which will be patented and eventually lead to a decrease in health costs in Australia. This research clearly falls under the national research priority of promoting and maintaining good health. Our findings are expected to benefit patients in addition to those suffering from AD, as pathocascades and pathogenic mechanisms are shared between a range of neurodegenerative disorders. Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE120102857
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Innovative chemical tools for the isolation, biochemical and structural analysis of biological macromolecular assemblies. This project will develop a new approach for determining the three dimensional structures of protein complexes. This project will demonstrate this approach by determining the structure of a protein complex involved in gene regulation and disease.
New insights into mammalian gene transcription - the role of parafibromin. Increasing our knowledge of fundamental gene and protein interactions is imperative as we move into an era of targetted molecular therapies to treat disease. Cancer is at the forefront of these diseases with hope of improved treatments firmly based in understanding the basic cell biology of tumours. This proposal describes research into a protein called parafibromin. We propose that parafibromin acts in major pathways res ....New insights into mammalian gene transcription - the role of parafibromin. Increasing our knowledge of fundamental gene and protein interactions is imperative as we move into an era of targetted molecular therapies to treat disease. Cancer is at the forefront of these diseases with hope of improved treatments firmly based in understanding the basic cell biology of tumours. This proposal describes research into a protein called parafibromin. We propose that parafibromin acts in major pathways responsible for how a cell manages stress by regulating levels of proteins involved in the cellular stress response. Discoveries made during the course of this research will provide knowledge of gene and protein interactions that will be important in the future to develop anti-cancer therapies. Read moreRead less
Identifying the pathways employed by growth hormone to regulate the proliferation of adult neural stem cells. As stem cells underpin the maintenance and regeneration of the brain and are known to decline in number and competence with age; understanding exactly how these cells are regulated is of broad national benefit. Furthermore, given the regulatory role of growth hormone throughout the body, insights gained from this project should lead to the discovery of novel therapeutic targets both with ....Identifying the pathways employed by growth hormone to regulate the proliferation of adult neural stem cells. As stem cells underpin the maintenance and regeneration of the brain and are known to decline in number and competence with age; understanding exactly how these cells are regulated is of broad national benefit. Furthermore, given the regulatory role of growth hormone throughout the body, insights gained from this project should lead to the discovery of novel therapeutic targets both within and outside the nervous system, ultimately leading to preventative and restorative strategies for maintaining good health. Finally, this Proposal is of significant national benefit as it will undoubtedly advance our knowledge base in stem cell biology, helping to maintain Australia as a global leader in stem cell research.Read moreRead less
Characterisation of a novel neural-specific ATPase in cholesterol transport. Ageing is determined by both genetic and metabolic factors. To a large part, the detailed mechanisms of ageing remain to be unexplored. Genetically, the timing of cell ageing entails the loss of telomeres (tips of chromosomes). However, the buildup of metabolic wastes resets the timing prematurely. Metabolic products accumulate from excess production or a shortfall of removal activity, which occurs in the various parts ....Characterisation of a novel neural-specific ATPase in cholesterol transport. Ageing is determined by both genetic and metabolic factors. To a large part, the detailed mechanisms of ageing remain to be unexplored. Genetically, the timing of cell ageing entails the loss of telomeres (tips of chromosomes). However, the buildup of metabolic wastes resets the timing prematurely. Metabolic products accumulate from excess production or a shortfall of removal activity, which occurs in the various parts of ageing cells in tissues such as brain. Traffic jams of cholesterol transport in the secretory pathway induce early ageing of the nerve cells. We investigate a novel mechanism controlling cholesterol transport in nerve cell ageing.Read moreRead less
Cellular Responses to Adversity: Oxidative Stress and Protection Against Oxidative Damage. A deficiency in the protein haem oxygenase-1 causes severe biological consequences in animals and humans. These include decreased reproduction, retarded development, the inability of the body to handle iron, chronic inflammation and increased susceptibility to age-associated diseases. This study will determine how a deficiency of the protein alters cells at the level of genes, proteins and protein function ....Cellular Responses to Adversity: Oxidative Stress and Protection Against Oxidative Damage. A deficiency in the protein haem oxygenase-1 causes severe biological consequences in animals and humans. These include decreased reproduction, retarded development, the inability of the body to handle iron, chronic inflammation and increased susceptibility to age-associated diseases. This study will determine how a deficiency of the protein alters cells at the level of genes, proteins and protein functions. By doing so, the project will illuminate how haem oxygenase-1 alters cell functions in a beneficial way. This information will eventually assist in preventing the serious disorders associated with deficiency of haem oxygenase-1. It will also provide the basis for novel treatments to slow down age-associated diseases.Read moreRead less
Molecular dynamics of steroid receptor crosstalk. This project uses state-of-the-art technology to show how steroids (for example, testosterone) affect many aspects of human life, and how these can be disrupted by chemicals and synthetic hormones. The results can be used to interpret disease, predict safety of new drugs, and to monitor risk to humans and wildlife of environmental chemicals.
Nuclear Trafficking of Apolipoprotein-E. Apolipoprotein-E (apoE) regulates specific age-related neurodegenerative and cardiovascular diseases. The role of apoE in these disorders is unclear. This project will benefit our community by providing the basic cell biology knowledge required to understand disease mechanisms and ultimately provide avenues for better treatments. Aspects of the project will focus on the modification of apoE by carbohydrates and the interaction of apoE with cellular carboh ....Nuclear Trafficking of Apolipoprotein-E. Apolipoprotein-E (apoE) regulates specific age-related neurodegenerative and cardiovascular diseases. The role of apoE in these disorders is unclear. This project will benefit our community by providing the basic cell biology knowledge required to understand disease mechanisms and ultimately provide avenues for better treatments. Aspects of the project will focus on the modification of apoE by carbohydrates and the interaction of apoE with cellular carbohydrate-containing structures. The importance of carbohydrates in the regulation of cellular and protein function is increasingly recognised and forms a foundation for the rapidly expanding discipline of glycobiology. This project will strengthen Australia's glycobiology research capacity.Read moreRead less