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.
Infertility affects one in six couples and is an extremely distressing, expensive and frustrating experience for those that it afflicts. Through gaining a better understanding of the molecular and cellular processes governing ovulation and early embryo development, this team will devise new therapeutic strategies to improve the reproductive health of Australian women.
Determinants Of Reproductive Health: Basic And Translational Studies In Fertility.
Funder
National Health and Medical Research Council
Funding Amount
$12,530,124.00
Summary
Reproductive health is an issue of national and international significance yet there are considerable unmet needs in the key areas of infertility and contraception. The health of each adult is strongly affected by very early events in development, including the effects of genetics and environment on sperm and eggs, and of the intra-uterine environment. This program will use a combination of advanced technologies to address these issues and will translate findings to the clinic, thus improving th ....Reproductive health is an issue of national and international significance yet there are considerable unmet needs in the key areas of infertility and contraception. The health of each adult is strongly affected by very early events in development, including the effects of genetics and environment on sperm and eggs, and of the intra-uterine environment. This program will use a combination of advanced technologies to address these issues and will translate findings to the clinic, thus improving the quality of reproductive health care and the long-term health of Australians.Read moreRead less
Periconceptual Foundations For A Healthy Start To Life.
Funder
National Health and Medical Research Council
Funding Amount
$11,022,802.00
Summary
Preconception and early pregnancy is a critical time for a women's health and that of her future child. New research suggests that a woman's genetic potential, her lifestyle and the physical and socioeconomic environment in which she lives, and her biological and social relationship with her male partner, all impact on the long term health of her baby. Abnormal events around the time of conception and in early pregnancy can predispose a newborn to later occurrence, in adult life, of conditions i ....Preconception and early pregnancy is a critical time for a women's health and that of her future child. New research suggests that a woman's genetic potential, her lifestyle and the physical and socioeconomic environment in which she lives, and her biological and social relationship with her male partner, all impact on the long term health of her baby. Abnormal events around the time of conception and in early pregnancy can predispose a newborn to later occurrence, in adult life, of conditions including heart disease, diabetes, obesity and stroke. These adverse events originate in the way that eggs and sperm develop, the uterus is prepared for implantation, the attachment of the early embryo to the lining of the uterus and subsequent growth of the placenta. This Program will study the early life events that promote or limit development of a baby's true potential for successful and healthy life. A better understanding of how lifestyle and environment interact with genes and biology to facilitate optimal growth of the fetus will underpin new preventative measures and therapeutic treatments for infertility, miscarriage and other reproductive disorders. The knowledge gained will inform health policy and clinical practise to improve reproductive health in all Australian women and promote healthy development in all Australian children. The team of researchers is a world-class group of clinicians, scientists and epidemiologists who have made major contributions to our understanding of this area. This team will interface with clinics and hospitals that engage with women prior to and during pregnancy, while having the influence to alter clinical and health practices as well as public health policies. The team will utilize the latest, most technologically advanced laboratory methods and clinical skills, including gene profiling, imaging of early pregnancy, randomised clinical trials and access to the best epidemiological and statistical assessments.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
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
Molecular Mechanisms In The Regulation Of Allergy And Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$4,977,215.00
Summary
To understand the fundamental cellular and molecular processes that underpin the development of allergic disorders, viral infections of the respiratory tract and chronic inflammatory diseases of the lung. There is particular interest in the role of immune cells, such T cells and granulocytes in these disorders, and in the processes that control their function. Understanding these processes will provide new insights into the immune system's role in health and disease, and help develop better ther ....To understand the fundamental cellular and molecular processes that underpin the development of allergic disorders, viral infections of the respiratory tract and chronic inflammatory diseases of the lung. There is particular interest in the role of immune cells, such T cells and granulocytes in these disorders, and in the processes that control their function. Understanding these processes will provide new insights into the immune system's role in health and disease, and help develop better therapies to treat inflammatory disorders.Read moreRead less