The Role Of ERK MAPKs In Compensated Cardiac Hypertrophy
Funder
National Health and Medical Research Council
Funding Amount
$241,650.00
Summary
According to recent statistics, heart failure accounts for almost 300 deaths each year in Australia. In fact, heart failure is now a major health problem that is on the rise, despite the reduced incidence of other forms of heart and blood vessel disease. We are now in the situation where the cost of treatment of heart failure exceeds that of treating all cancer patients, and there are more patient days in hospital with heart failure than with any other heart or blood vessel disease. Most often, ....According to recent statistics, heart failure accounts for almost 300 deaths each year in Australia. In fact, heart failure is now a major health problem that is on the rise, despite the reduced incidence of other forms of heart and blood vessel disease. We are now in the situation where the cost of treatment of heart failure exceeds that of treating all cancer patients, and there are more patient days in hospital with heart failure than with any other heart or blood vessel disease. Most often, the heart fails to act as an effective pump following long-term exposure to high blood pressure. The increased work load placed on the heart effectively forces it to increase in size in a process called cardiac hypertrophy. But this initial compensation which is of benefit to the patient commonly deteriorates and many of the heart cells die. The resulting death of heart cells is the failure of the heart, and death of the patient is inevitable. The fundamental changes in the functional protein molecules of the heart cells that accompany hypertrophy and heart failure are likely to be extremely complex. As yet, no research has taken a global and unbiased look into this complexity. However, there are new technologies that allow us to take such a look. We have established a collaborative research team to investigate the fundamental mechanisms underlying cardiac hypertrophy. We are exploiting a novel model in which hypertrophy does not progress to failure. Our combined expertise allows us to use recently developed scientific methodologies to evaluate the biochemical basis for these events in the heart. We have chosen to focus on documenting the changes in proteins that accompany cardiac hypertrophy with the aim to establish important targets for interventions to permit cardiac cells to survive despite hypertrophy. This will have important implications for preventing cardiac failure.Read moreRead less
Function Of The S100A1 Ca2+-binding Protein Under Physiological And Pathological Conditions
Funder
National Health and Medical Research Council
Funding Amount
$452,545.00
Summary
The S100A1 protein is one of the most abundant proteins in human heart muscle cells. It binds calcium ions and may play a role in the regulation of heart function. S100A1 levels are reduced in human heart failure, but it is unclear whether this reduction contributes to worsening of the disease. To study this, we have generated a genetically modified mouse strain that cannot make the S100A1 protein. We will use these mice to study how important the protein is for heart function under normal condi ....The S100A1 protein is one of the most abundant proteins in human heart muscle cells. It binds calcium ions and may play a role in the regulation of heart function. S100A1 levels are reduced in human heart failure, but it is unclear whether this reduction contributes to worsening of the disease. To study this, we have generated a genetically modified mouse strain that cannot make the S100A1 protein. We will use these mice to study how important the protein is for heart function under normal conditions, and how it contributes to the development of heart failure. Preliminary data indicate that adult mice with reduced S100A1 protein levels develop a form of heart disease that significantly reduces the efficiency of the pump function of the heart.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
Inhibition of pro-inflammatory cytokine secretion- A new route to therapeutics of chronic inflammatory disease. Chronic inflammatory diseases, including rheumatoid arthritis and inflammatory bowel disease, affect millions of people leading to considerable suffering, economic loss and premature death. Anti-TNF treatments have recently shown success in the treatment of rheumatoid arthritis, inflammatory bowel disease and other conditions, however, a substantial number of patients (~50%) do not re ....Inhibition of pro-inflammatory cytokine secretion- A new route to therapeutics of chronic inflammatory disease. Chronic inflammatory diseases, including rheumatoid arthritis and inflammatory bowel disease, affect millions of people leading to considerable suffering, economic loss and premature death. Anti-TNF treatments have recently shown success in the treatment of rheumatoid arthritis, inflammatory bowel disease and other conditions, however, a substantial number of patients (~50%) do not respond to the current TNF treatments. Improved anti-TNF strategies would provide enhanced health outcomes and welcome relief to many Australians. In addition, the economic benefit of the TNF market is very substantial. Therefore the potential impact of this research is very high both for health care and economical potential.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0882890
Funder
Australian Research Council
Funding Amount
$130,000.00
Summary
Investigating protein/protein interactions. To establish and maintain a prominent position in scientific research, Australian scientists must have access to state of the art technology. The Bio21 Institute is a multidisciplinary research centre specialising in medical agricultural and environmental science and is ideally suited to house an SPR facility. SPR provides unique functional, kinetic and thermodynamic information on molecular interactions which give rise to both physiological and path ....Investigating protein/protein interactions. To establish and maintain a prominent position in scientific research, Australian scientists must have access to state of the art technology. The Bio21 Institute is a multidisciplinary research centre specialising in medical agricultural and environmental science and is ideally suited to house an SPR facility. SPR provides unique functional, kinetic and thermodynamic information on molecular interactions which give rise to both physiological and pathological outcomes. A detailed knowledge of molecular interactions is fundamental to the understanding of all biological systems. When placed at the Bio21 Institute, the facility will foster the development of diversified collaborations between the applicants and the wider research community.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.
Novel cellular functions of the microtubule-associated protein tau: Physiological and pathological implications. The social and economic burden of Alzheimer's disease (AD) is enormous, and by 2040 more than 500,000 Australians will suffer from this disease. A key histopathological hallmark of this and many other related diseases are insoluble deposits of the protein tau. Research into novel functions of tau in signalling and transport (both of which are heavily compromised in diseased brains) wi ....Novel cellular functions of the microtubule-associated protein tau: Physiological and pathological implications. The social and economic burden of Alzheimer's disease (AD) is enormous, and by 2040 more than 500,000 Australians will suffer from this disease. A key histopathological hallmark of this and many other related diseases are insoluble deposits of the protein tau. Research into novel functions of tau in signalling and transport (both of which are heavily compromised in diseased brains) will be followed directly by assay development for tau-directed drug screening. The national benefit of this research is manifold by (a) patenting new data, (b) developing treatment strategies for an un-curable disease, and (c) establishing links to the growing Australian biotech industry (in addition to existing links to international pharmaceutical companies).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
To investigate the role of the protein kinase SMG-1 in the stress response. This project is included in the designated priority area of research Promoting and Maintaining Good Health and Ageing Well. It represents a mouse model to assist in the study of human disease. It is the first mouse model for SMG-1, a protein kinase that protects against a variety of different forms of stress. The strength of the model is that it can be combined with other mouse models to interrogate and elucidate the eve ....To investigate the role of the protein kinase SMG-1 in the stress response. This project is included in the designated priority area of research Promoting and Maintaining Good Health and Ageing Well. It represents a mouse model to assist in the study of human disease. It is the first mouse model for SMG-1, a protein kinase that protects against a variety of different forms of stress. The strength of the model is that it can be combined with other mouse models to interrogate and elucidate the events occurring in different pathways for stress. The expectation is that ground-breaking data will be generated with this model providing scientific leadership on the role of this protein. It will also assist in establishing new collaborations.Read moreRead less