A Novel Lipid Sensitive Kinase And Its Role In Obesity-induced Inflammation And Insulin Resistance.
Funder
National Health and Medical Research Council
Funding Amount
$560,045.00
Summary
It is now apparent that obesity leads to chronic low grade inflammation which results in insulin resistance or pre-diabetes. The mechanisms that link obesity-induced inflammation to insulin resistance are not well understood, but involve lipid oversupply. We have preliminary data identifying that a protein, not known to previously play a role in metabolic diseases, is a critical mediator of lipid-induced inflammation. We will investigate the clinical potential of blocking this protein.
Regulation of lipolysis: new players, new paradigms. The way in which fat is broken down is poorly understood. This research will determine how important proteins in fat breakdown are turned on and off. By understanding this relationship, effective pharmaceutical treatments will be developed that will enhance the capacity to burn fat and ultimately reduce the incidence of type 2 diabetes and cardiovascular disease, and ease the associated financial burden on the community and healthcare system. ....Regulation of lipolysis: new players, new paradigms. The way in which fat is broken down is poorly understood. This research will determine how important proteins in fat breakdown are turned on and off. By understanding this relationship, effective pharmaceutical treatments will be developed that will enhance the capacity to burn fat and ultimately reduce the incidence of type 2 diabetes and cardiovascular disease, and ease the associated financial burden on the community and healthcare system. Understanding fat breakdown is also important for developing new processing technologies in the food industry.Read moreRead less
Molecular basis of skeletal muscle lipoapoptosis. High levels of fat in cells are associated with obesity and type 2 diabetes, medical conditions that have increased dramatically in prevalence in Australia. High fat levels in cells also causes cell death. This research will determine the mechanisms by which excessive fat storage leads to cell death and whether this leads to insulin resistance and type 2 diabetes. By understanding this relationship, effective pharmaceutical treatments will be dev ....Molecular basis of skeletal muscle lipoapoptosis. High levels of fat in cells are associated with obesity and type 2 diabetes, medical conditions that have increased dramatically in prevalence in Australia. High fat levels in cells also causes cell death. This research will determine the mechanisms by which excessive fat storage leads to cell death and whether this leads to insulin resistance and type 2 diabetes. By understanding this relationship, effective pharmaceutical treatments will be developed that will ultimately reduce the incidence of type 2 diabetes, and ease the associated financial burden on the community and healthcare system.Read moreRead less
Understanding the critical processes that control cell death and using this knowledge to kill cells that have evaded death. Cell death is essential for protecting the body against cancer, and defects in cell death pathways contribute to cancer progression. To design new and better cancer therapies we must understand the critical processes which control cell death, and develop effective ways to either reset, or bypass, defects in cell death pathways that contribute to cancer. The program as outl ....Understanding the critical processes that control cell death and using this knowledge to kill cells that have evaded death. Cell death is essential for protecting the body against cancer, and defects in cell death pathways contribute to cancer progression. To design new and better cancer therapies we must understand the critical processes which control cell death, and develop effective ways to either reset, or bypass, defects in cell death pathways that contribute to cancer. The program as outlined will elucidate the process of mitochondrial outer membrane permeabilization, a critical event in cell death by apoptosis, and determine how to kill cells in which this event is blocked.Read moreRead less
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
Regulatory mechanisms in skeletal muscle lipid hydrolysis. The regulation of intramuscular triglyceride (fat) utilisation by human skeletal muscle is largely unknown. Our contention is that the specialized protein enzyme, hormone sensitive lipase (HSL), has a fundamental role in intramuscular triacylglycerol utilisation and is regulated by both intramuscular levels of key metabolites and circulating hormone concentrations. We also propose control points subsequent to HSL activation are important ....Regulatory mechanisms in skeletal muscle lipid hydrolysis. The regulation of intramuscular triglyceride (fat) utilisation by human skeletal muscle is largely unknown. Our contention is that the specialized protein enzyme, hormone sensitive lipase (HSL), has a fundamental role in intramuscular triacylglycerol utilisation and is regulated by both intramuscular levels of key metabolites and circulating hormone concentrations. We also propose control points subsequent to HSL activation are important for triglyceride hydrolysis. Our proposed project examines these factors and will enhance our understanding of the regulation of muscle fat use, thereby leading to potential metabolic strategies (nutritional, pharmacological) that enhance skeletal muscle function at rest and during exercise.Read moreRead less
Interplay Between Metabolic Reprogramming And Oncogenic Signalling In The Cellular Response To Chemotherapy
Funder
National Health and Medical Research Council
Funding Amount
$654,035.00
Summary
Chemotherapy resistance is a major barrier to the treatment of triple-negative breast cancer (TNBC). We seek to uncover an intimate link between cell metabolism and oncogenic signalling pathways in regulating the cellular response to chemotherapy. Our studies will identify a critical mechanism limiting the therapeutic efficacy of chemotherapy and investigate combination therapy strategies that could improve the treatment of TNBC.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE150100004
Funder
Australian Research Council
Funding Amount
$540,000.00
Summary
An automated 3D electron microscopy facility. An automated 3D electron microscopy facility: The aim of this project is to establish the next generation of electron microscopy facility, with a fully automated tool enabling 3D imaging. The automated serial section system incorporated in a scanning electron microscope circumvents the limitation of transmission electron microscopy, which provides unique insights into molecular structures and cell components at high resolution, however, the area and ....An automated 3D electron microscopy facility. An automated 3D electron microscopy facility: The aim of this project is to establish the next generation of electron microscopy facility, with a fully automated tool enabling 3D imaging. The automated serial section system incorporated in a scanning electron microscope circumvents the limitation of transmission electron microscopy, which provides unique insights into molecular structures and cell components at high resolution, however, the area and volume are limited in size to a few microns. This new type of microscope can image whole organisms and be used by non-electron microscopists. It will be housed in an open access facility and will meet a growing demand for 3D electron microscopy.Read moreRead less
Cytopathological roles of AMPK in mitochondrial dysfunction. This research project will benefit the Australian community by deepening our understanding of mitochondrial and neurodegenerative diseases. These diseases are incurable and treatment options are limited. The knowledge gained in this project should assist in the development of new or improved treatments. The project will also contribute to the training of young scientists in biomedical research and will enhance Australia's international ....Cytopathological roles of AMPK in mitochondrial dysfunction. This research project will benefit the Australian community by deepening our understanding of mitochondrial and neurodegenerative diseases. These diseases are incurable and treatment options are limited. The knowledge gained in this project should assist in the development of new or improved treatments. The project will also contribute to the training of young scientists in biomedical research and will enhance Australia's international scientific reputation because it involves a significant and novel biomedical discovery.
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Reducing the fat burden: Identification of novel cellular and molecular targets for alleviating skeletal muscle insulin resistance. Insulin resistance and the associated consequences are a major public health problem in Australia and cost the healthcare system >$1.1 billion/year. Exercise training and thiaziolidinedione (TZD) treatment are therapies that partially ameliorate insulin resistance through distinct and independent mechanisms. However, neither intervention represents a viable long-ter ....Reducing the fat burden: Identification of novel cellular and molecular targets for alleviating skeletal muscle insulin resistance. Insulin resistance and the associated consequences are a major public health problem in Australia and cost the healthcare system >$1.1 billion/year. Exercise training and thiaziolidinedione (TZD) treatment are therapies that partially ameliorate insulin resistance through distinct and independent mechanisms. However, neither intervention represents a viable long-term strategy: exercise training has low compliance, while chronic TZD use is associated with several adverse side effects (edema, weight gain etc.). We will investigate the metabolic, cellular and molecular mechanisms by which these therapies each exert their positive effect on insulin action with the aim of identifying novel targets for future drug interventions. Read moreRead less