Targeting genes elevated in the athlete's heart to improve function of the failing heart. Cardiovascular disease affects about 3.7 million Australians and heart failure ranks as one of the major killers, representing a huge burden on our health care system and economy. This situation is likely to get worse with an increasing ageing population. Current therapeutics for heart failure patients largely delay disease progression but generally fail in significantly improving heart function and quality ....Targeting genes elevated in the athlete's heart to improve function of the failing heart. Cardiovascular disease affects about 3.7 million Australians and heart failure ranks as one of the major killers, representing a huge burden on our health care system and economy. This situation is likely to get worse with an increasing ageing population. Current therapeutics for heart failure patients largely delay disease progression but generally fail in significantly improving heart function and quality of life. The proposal has focused on targeting the protective effects of 'good' heart growth by identifying genes elevated in the heart in response to exercise. Targeting genes elevated in the athlete's heart to improve function of the failing heart represents a new strategy for the treatment of heart failure.Read moreRead less
The Genetic Analysis of Neurological Diseases. Multiple sclerosis and Parkinson's are debilitating neurodegenerative diseases, which affect 16,000 and 80,000 Australians, respectively. Between them, these diseases cost the community $7.8 billion per annum, and there is no cure. This proposal will study the genes that influence a person's predisposition to developing these diseases, and what makes some people have particular characteristics. It will provide novel insights into the diseases themse ....The Genetic Analysis of Neurological Diseases. Multiple sclerosis and Parkinson's are debilitating neurodegenerative diseases, which affect 16,000 and 80,000 Australians, respectively. Between them, these diseases cost the community $7.8 billion per annum, and there is no cure. This proposal will study the genes that influence a person's predisposition to developing these diseases, and what makes some people have particular characteristics. It will provide novel insights into the diseases themselves and information that could help in the development of new and more effective drugs, and biomarkers to assist in the prediction of prognosis. Such advances would decrease the economic impact of these diseases and improve quality of life for those affected.Read moreRead less
Age and Gender Related Changes in Motor Control of the Upper Airway Muscle Genioglossus During Sleep. Obstructive Sleep Apnoea (OSA) is the repetitive obstruction of the airway during sleep. Obstructions occur because muscles of the upper airway fail to keep the airway open during inspiration. The disorder is associated with cardiovascular disease and cognitive and behavioural impairment. The prevalence of the disorder increases in older adults, contributing to age-related health and behavioural ....Age and Gender Related Changes in Motor Control of the Upper Airway Muscle Genioglossus During Sleep. Obstructive Sleep Apnoea (OSA) is the repetitive obstruction of the airway during sleep. Obstructions occur because muscles of the upper airway fail to keep the airway open during inspiration. The disorder is associated with cardiovascular disease and cognitive and behavioural impairment. The prevalence of the disorder increases in older adults, contributing to age-related health and behavioural problems. However, age-related changes differ in men and women. We believe the high prevalence of OSA in older adults is due to age and gender related changes in the activity of muscles in the upper airway. We will study the behaviour of the upper airway muscle genioglossus during sleep in young, middle-aged and older men and women.Read moreRead less
Investigation of the function of Sel S a novel selenoprotein. The long term aim of this project is to find a way to prevent or delay the onset of both Type 1 and Type 2 diabetes. ChemGenex pharmaceuticals, our commercial partners have discovered and patented a selenoprotein with antioxidant properties and have shown in vitro that it protects insulin-producing beta cells from oxidative damage. This project aims to prove, in an in vivo setting, that this protein can prevent or delay the onset of d ....Investigation of the function of Sel S a novel selenoprotein. The long term aim of this project is to find a way to prevent or delay the onset of both Type 1 and Type 2 diabetes. ChemGenex pharmaceuticals, our commercial partners have discovered and patented a selenoprotein with antioxidant properties and have shown in vitro that it protects insulin-producing beta cells from oxidative damage. This project aims to prove, in an in vivo setting, that this protein can prevent or delay the onset of diabetes in mouse models of type 1 and Type 2 diabetes.Read moreRead less
The ApoE Interactome in Human Plasma. In this, the post-genome era, the emphasis has switched from the delineation of genome structure to the tremendous task of characterizing the gene products. One of the important aspects evolving in this new era is the design of strategies that enable identification of global protein-protein interactions, defined by the Human Proteome Organisation as the interactome. This, the apoE interactome in human plasma project, will identify novel interactions between ....The ApoE Interactome in Human Plasma. In this, the post-genome era, the emphasis has switched from the delineation of genome structure to the tremendous task of characterizing the gene products. One of the important aspects evolving in this new era is the design of strategies that enable identification of global protein-protein interactions, defined by the Human Proteome Organisation as the interactome. This, the apoE interactome in human plasma project, will identify novel interactions between plasma proteins and apoE, which is a lipid-binding protein genetically linked to age-related diseases affecting more than 500,000 Australians. This project will therefore provide scope for novel treatments and early detection of disease, namely cardiovascular and Alzheimer's disease.Read moreRead less
Regulating calcium handling in skeletal muscle - implications for muscle contraction, injury and repair, ageing and development. Understanding the mechanisms regulating calcium in skeletal muscle has important relevance for studying muscle growth and development, injury and repair, and for identifying therapeutic targets and potential therapies for ageing-related disorders, reconstructive surgery, sporting and workplace injuries, and muscle diseases. Combining cell physiology, fluorescence micro ....Regulating calcium handling in skeletal muscle - implications for muscle contraction, injury and repair, ageing and development. Understanding the mechanisms regulating calcium in skeletal muscle has important relevance for studying muscle growth and development, injury and repair, and for identifying therapeutic targets and potential therapies for ageing-related disorders, reconstructive surgery, sporting and workplace injuries, and muscle diseases. Combining cell physiology, fluorescence microscopy and digital imaging technologies for studying multicellular tissues such as skeletal muscle will enhance the international competitiveness of Australian biological research. The research will optimise development of gene delivery systems that may find eventual application for muscle wasting disorders and conditions where muscle weakness compromises quality of life.Read moreRead less
A redox sensor and triple receptor function for guanylyl cyclase. Nitric oxide (NO) protects from blood vessel spasms and clot formation. Conversely, insufficient NO occurs in cardiovascular disease. Life-saving drugs like glycerol trinitrate supply more NO to blood vessels, however these drugs are limited in their action when their target protein (NOGC) is decreased or defective, eg. in hypertension or arteriosclerosis. We have elucidated the reason for this defect and simultaneously discovered ....A redox sensor and triple receptor function for guanylyl cyclase. Nitric oxide (NO) protects from blood vessel spasms and clot formation. Conversely, insufficient NO occurs in cardiovascular disease. Life-saving drugs like glycerol trinitrate supply more NO to blood vessels, however these drugs are limited in their action when their target protein (NOGC) is decreased or defective, eg. in hypertension or arteriosclerosis. We have elucidated the reason for this defect and simultaneously discovered an entirely novel group of drugs which activate NOGC without NO. Impressively, these drugs are most effective in diseased blood vessels. The aim is the development of novel blood pressure lowering/anti-anginal drugs with higher effectiveness and less side-effects because they work in an entirely new way.Read moreRead less
Novel roles for importin alpha proteins in the nucleus. The project will provide fundamental new information about how changes in cell function are influenced by importin (IMP) alpha proteins, both through changes in gene transcription and through alterations to intracellular transport. These findings will inform areas of national priority that include Aging Well, Aging Productively with specific regard to cellular stress responses, and A Healthy Start to Life in the context of production of hea ....Novel roles for importin alpha proteins in the nucleus. The project will provide fundamental new information about how changes in cell function are influenced by importin (IMP) alpha proteins, both through changes in gene transcription and through alterations to intracellular transport. These findings will inform areas of national priority that include Aging Well, Aging Productively with specific regard to cellular stress responses, and A Healthy Start to Life in the context of production of healthy, genetically intact sperm. This project draws together an international team to investigate a phenomenon with implications for new understanding of normal developmental processes and the response of cells/tissues to disease conditions.Read moreRead less
Identification of genes regulating breast cancer progression and metastasis. Breast cancer is the most common cause of cancer-related death in women in Australia. Although the treatments have improved over the last thirty years, many women still die from relapse of the disease. Our goal is to identify genes involved in the regulation of breast cancer progression and metastasis. This may lead to the discovery of druggable molecules for better targeted therapies for patients.
Theoretical studies of molecular mechanisms of abnormal protein aggregation. Many proteins undergo conformational change and association as part of their physiological behavior. However, some proteins share a tendency to abnormal aggregation and form amyloid fibrils leading to disorders such as Alzheimer's and variant Creutzfeldt-Jacob diseases. Insulin, one such protein, has a high propensity to aggregate and form fibrils creating difficulties in preparation, storage and application. Using adva ....Theoretical studies of molecular mechanisms of abnormal protein aggregation. Many proteins undergo conformational change and association as part of their physiological behavior. However, some proteins share a tendency to abnormal aggregation and form amyloid fibrils leading to disorders such as Alzheimer's and variant Creutzfeldt-Jacob diseases. Insulin, one such protein, has a high propensity to aggregate and form fibrils creating difficulties in preparation, storage and application. Using advanced theoretical modelling techniques we will gain insight into the molecular mechanism of fibrillation by investigating the formation of insulin aggregates. An improved understanding of the essential mechanism of protein aggregation will allow the rational design of new drugs.Read moreRead less