A Program Of Research Addressing The Transition From Health To Advanced Cardiovascular Disease.
Funder
National Health and Medical Research Council
Funding Amount
$13,017,057.00
Summary
Cardiovascular disease (CVD) is the major cause of death and disability in Australia and worldwide. This burden will increase without new knowledge. We will address knowledge gaps that delay more effective prevention and control. Our team has a strong track record of influencing clinical practice of CVD prevention, treatment and technology transfer. For many, the first indication of a heart problem is sudden heart attack or death. By understanding mechanisms we aim to develop new tests and treat ....Cardiovascular disease (CVD) is the major cause of death and disability in Australia and worldwide. This burden will increase without new knowledge. We will address knowledge gaps that delay more effective prevention and control. Our team has a strong track record of influencing clinical practice of CVD prevention, treatment and technology transfer. For many, the first indication of a heart problem is sudden heart attack or death. By understanding mechanisms we aim to develop new tests and treatments that prevent heart attack, heart failure and other serious consequences of atherosclerosis.Read moreRead less
Regulation Of Neural Cell Production In The Normal And Diseased Brain
Funder
National Health and Medical Research Council
Funding Amount
$6,888,658.00
Summary
Members of this team are at the forefront of research into the molecular control of nerve cell production and function in the developing and adult brain. They were responsible, often through collaboration, for many of the major discoveries demonstrating that stem cells in the brain of adult animals can generate new nerve cells; this revolutionised our concept of the brain and opened-up the possibility of therapeutic repair of neural damage through stimulation of a patient?s own stem cells. Disco ....Members of this team are at the forefront of research into the molecular control of nerve cell production and function in the developing and adult brain. They were responsible, often through collaboration, for many of the major discoveries demonstrating that stem cells in the brain of adult animals can generate new nerve cells; this revolutionised our concept of the brain and opened-up the possibility of therapeutic repair of neural damage through stimulation of a patient?s own stem cells. Discovering the molecular mechanisms controlling this process is the goal of the present program. In order to achieve this aim we have formed a team on the basis of considerable past success, as well as future requirements. The team members have the complementary skills to assess all aspects of the problem, including crucial functional and clinical expertise. By combining resources we will position ourselves at the very forefront of the international competition to discover and to evaluate clinically the molecular mechanisms underlying neural repair and regeneration. This is of enormous significance in determining how we best treat stroke, injury and other neurodegenerative diseases in the next 10 years, and will lead to the development of new therapeutics of immense value. The team will use innovative approaches such as cell-sorting to obtain pure populations of stem cells and their progeny in order to identify new therapeutic targets; these will then be validated in animal models of neurological disease. Since team members have previously been involved in progressing molecular discovery to clinical trials, we are also in a good position to exploit these discoveries in partnership with the biopharmaceutical industry.Read moreRead less
Roles Of Impaired Apoptosis And Differentiation In Tumourigenesis And Therapy
Funder
National Health and Medical Research Council
Funding Amount
$21,656,910.00
Summary
The ten scientific laboratories in this program have joined forces to investigate two ways in which tumours develop. Both are of particular interest, because they suggest new ways in which cancer might be overcome. Most of our tissues are continually renewed throughout life by production of new cells. Therefore many of the old cells in each tissue must die off to maintain the proper cell numbers. To eliminate cells that are no longer needed or have become damaged, the body has developed a remark ....The ten scientific laboratories in this program have joined forces to investigate two ways in which tumours develop. Both are of particular interest, because they suggest new ways in which cancer might be overcome. Most of our tissues are continually renewed throughout life by production of new cells. Therefore many of the old cells in each tissue must die off to maintain the proper cell numbers. To eliminate cells that are no longer needed or have become damaged, the body has developed a remarkable cell suicide process termed apoptosis. Unfortunately, however, occasionally a random accident to the genes in one of our cells prevents the machinery for apoptosis from being turned on. In that case, the cell will not die when it should and, by continually dividing, it may eventually give rise to a cancer. Since most cancer cells still retain most of the machinery for apoptosis, however, a drug that could switch on this natural cell death machinery would provide a promising new approach to cancer therapy. Identifying and developing such drugs is one major long-term goal of this program. The other focus of our program concerns stem cells. These are rare cells with the remarkable ability to generate an entire tissue. For example, one of our laboratories has identified stem cells that can generate all the cells in the breast. The almost unlimited regenerative capacity of stem cells has a built-in danger. If a stem cell acquires the ability to proliferate excessively, it can go on to form a tumour. Indeed, many cancer researchers now suspect that rare stem cells within a tumour cause its inexorable growth. If tumour growth is maintained by stem cells, it will be essential to develop new forms of therapy that target these rare cancer stem cells rather than merely the bulk of the tumour cells. This is another key long-term goal of our program.Read moreRead less
Novel Therapeutic Strategies To Reduce The Burden Of Chronic Heart Failure
Funder
National Health and Medical Research Council
Funding Amount
$4,928,323.00
Summary
The broad aims of the Program are to develop novel strategies in the prevention and treatment of chronic heart failure. This will involve investigating new targets for pharmacological therapies, evaluating whether common co-morbid disease states such as diabetes alter the efficacy of these therapies and investigating the role of stem-cell therapy in this setting. The Program will also evaluate the contribution of non-heart failure drugs to the burden of heart failure, determine the impact of rur ....The broad aims of the Program are to develop novel strategies in the prevention and treatment of chronic heart failure. This will involve investigating new targets for pharmacological therapies, evaluating whether common co-morbid disease states such as diabetes alter the efficacy of these therapies and investigating the role of stem-cell therapy in this setting. The Program will also evaluate the contribution of non-heart failure drugs to the burden of heart failure, determine the impact of rurality on prescribing for this condition and explore systems of optimising delivery of best practice to the community. This research formalises the existing collaborative efforts of a team of investigators that span all aspects of research into the therapeutics of CHF from basic laboratory research to evaluation of patients in clinical trials and public health translational aspects of this condition. The Chief Investigators and Principal Investigators have an existing successful research collaboration which will be greatly expanded via Program.Read moreRead less
Molecular Mechanisms Of Cardiac Function And Disease
Funder
National Health and Medical Research Council
Funding Amount
$8,213,642.00
Summary
Heart disease remains the leading cause of death in our society. Almost two million Australians suffer from the debilitating effects of heart disease and it is the leading cause of premature permanent disability in our workers. Heart defects are also the most common type of birth defect and the leading cause of deaths in infants dying from birth defects. Many of these problems can be attributed directly to defects in the development, repair and-or function of heart muscle and, at the cellular le ....Heart disease remains the leading cause of death in our society. Almost two million Australians suffer from the debilitating effects of heart disease and it is the leading cause of premature permanent disability in our workers. Heart defects are also the most common type of birth defect and the leading cause of deaths in infants dying from birth defects. Many of these problems can be attributed directly to defects in the development, repair and-or function of heart muscle and, at the cellular level, of heart muscle cells or cardiomyocytes. Understanding the cardiomyocyte as well as integrated heart development, biology, physiology and function, therefore, holds great promise for major advances in the prevention and treatment of contemporary heart diseases. This Program Grant brings together a unique team of interactive researchers with expertise in cardiovascular physiology, as well as developmental, cellular and molecular biology. The outcomes anticipated from new insights into heart biology that will result from the proposed studies, are the development of novel therapeutic approaches for the prevention and treatment of heart attacks and heart failure.Read moreRead less
Innovative Stem Cell-based Strategies To Establish Immune Tolerance And Tissue Repair
Funder
National Health and Medical Research Council
Funding Amount
$5,554,618.00
Summary
Diseases such as autoimmune gastritis, multiple sclerosis and diabetes arise because a rogue immune system has turned inwards to attack our organs. The organ destruction follows from recognition by the immune system of specific molecules in these organs. These autoimmune diseases are incurable and controlled mainly by long-term administration of substances that suppress the immune system, often with serious side-effects. A rational approach is to render the rogue immune system harmless by removi ....Diseases such as autoimmune gastritis, multiple sclerosis and diabetes arise because a rogue immune system has turned inwards to attack our organs. The organ destruction follows from recognition by the immune system of specific molecules in these organs. These autoimmune diseases are incurable and controlled mainly by long-term administration of substances that suppress the immune system, often with serious side-effects. A rational approach is to render the rogue immune system harmless by removing the cells that recognize these particular molecules. This can be achieved by a Trojan horse approach in which the molecules are delivered to the immune system such that that the immune cells that recognize them are removed. To deliver these molecules to the immune system we will genetically engineer bone marrow stem cells, or embryonic stem cells that generate these stem cells, because they are precursors of mature immune cells. Rejection of organ transplants arise in a similar way and also require long-term immunosuppression. A similar approach can therefore be taken to promote acceptance of foreign organ grafts. In the aged, we will combine these approaches with rejuvenation of the immune system by blockade of sex steroid production and-or by creation of a new immune organ.Read moreRead less
Colorectal Cancer - Molecular Basis To Targeted Therapeutics.
Funder
National Health and Medical Research Council
Funding Amount
$19,818,386.00
Summary
Cancer of the colon and rectum is the most common form of cancer in Australia. Over 12,000 people are diagnosed each year with colorectal cancer (CRC) and more than one third of people will die of their disease. CRC is caused by mistakes in production of colon cells. Our research aims to discover new ways to detect CRC, develop smart drugs and nanoparticle delivery systems for destroying all types of CRC cells. We will then test our new anti-cancer drugs in clinical trials with CRC patients.
Molecular And Cellular Studies Of The Adaptive Immune Response In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$16,509,154.00
Summary
Immune responses protect us against pathogens such as viruses and bacteria. However inappropriate immune responses can result in autoimmune conditions such as systemic lupus erythmatosus, multiple sclerosis, type I diabetes, asthma as well as immunodeficiencies. The aim of our proposal is to gain a thorough understanding of how all the cells of the immune system function and interact with each other, and what goes wrong when inflammatory diseases develop. We plan to do this using state-of-of-the ....Immune responses protect us against pathogens such as viruses and bacteria. However inappropriate immune responses can result in autoimmune conditions such as systemic lupus erythmatosus, multiple sclerosis, type I diabetes, asthma as well as immunodeficiencies. The aim of our proposal is to gain a thorough understanding of how all the cells of the immune system function and interact with each other, and what goes wrong when inflammatory diseases develop. We plan to do this using state-of-of-the-art technologies, including genetically modified mice, gene microarrays, monoclonal antibodies, and flow cytometry. We have brought together Australia's leading immunologists with complimentary expertise and research interests in specific areas of immunology including cytokines, cell migration, inflammatory diseases, autoimmunity and cell-cell interactions. One aspect of the application is to understand the genetic and molecular basis of immunological diseases. However we also wish to move on from an understanding to treatment of immunological diseases through the development of novel therapeutics. We will form collaborations with biotech and pharmaceutical companies (including our own spin off companies) to advance important new therapeutics for autoimmune and allergic diseases. These conditions represent a significant health burden to Australia.Read moreRead less
This program brings together a team of researchers from The Walter and Eliza Hall Institute of Medical Research to study how the body regulates antibody production to fight disease. Antibodies are made by B-cells and are essential for a functional immune system. B cells circulate in the body, searching for signs of infection. When they encounter an invader, they mature, with the help of other immune cells, into antibody-producing cells. A small proportion of the cells are set aside as _memory� c ....This program brings together a team of researchers from The Walter and Eliza Hall Institute of Medical Research to study how the body regulates antibody production to fight disease. Antibodies are made by B-cells and are essential for a functional immune system. B cells circulate in the body, searching for signs of infection. When they encounter an invader, they mature, with the help of other immune cells, into antibody-producing cells. A small proportion of the cells are set aside as _memory� cells that can rapidly become antibodyproducing cells should the same infection occur again in the future. This is the basis of vaccination. This program aims to understand how a B cell changes into an antibody-producing cell, by studying the genes that are known to be required for the cells to form, or to do their work. We will study animals whose immune systems are under- or over-active, to find out what part of the antibody-producing process is faulty. Using this information, we hope eventually to be able to study diseases of antibody producing cells in humans (as occur in allergy, asthma, rheumatoid arthritis and leukaemia), to be able to identify the precise cause of the problem, and to suggest a therapy. This information may also be used to improve the outcome of vaccination where an enhanced antibody response is desired.Read moreRead less