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The team has been at the forefront of research on type 1 diabetes for over a decade. This form of diabetes is a major chronic disease from childhood, as well as accounting for at least 10% of adult-onset diabetes. It occurs when the body�s immune system attacks and destroys the beta cells in the pancreas that make insulin, the hormone that controls the level of glucose in the blood. The team was one of the first in the world, and is the only one in Australia, to develop screening programs to tes ....The team has been at the forefront of research on type 1 diabetes for over a decade. This form of diabetes is a major chronic disease from childhood, as well as accounting for at least 10% of adult-onset diabetes. It occurs when the body�s immune system attacks and destroys the beta cells in the pancreas that make insulin, the hormone that controls the level of glucose in the blood. The team was one of the first in the world, and is the only one in Australia, to develop screening programs to test and identify people at risk for type 1 diabetes. They showed that the underlying disease could start years before symptoms occurred and discovered genes that determine the rate at which the underlying disease progresses. They have also found evidence that the disease may be triggered by gut viruses called rotaviruses in genetically-susceptible individuals. They showed that type 1 diabetes could be prevented in a mouse model by getting the immune system to make a protective response to insulin, and then went on to apply this in at-risk humans in a controlled trial of intranasal insulin, the first of its kind. They have used genetic techniques not only to pinpoint the mechanisms responsible for killing the beta cells but also to modify the beta cells to make them resistant to attack by these mechanisms. The multidisciplinary approach of the team will be directed to further understanding the genetic and environmental factors underlying type 1 diabetes and the immune mechanisms, particularly involving special white blood cells called T cells, that kill beta cells. A molecular target of the immune attack, the parent of insulin called proinsulin, will be used, paradoxically, as a tool to regulate the immune system and avert the attack. This will be achieved by giving proinsulin via the mucosa of the naso-respiratory tract or via the bone marrow-derived stem cells, initiallyin the mouse model as a test of feasibility for human application. In parallel with these approaches to prevention, specially constructed viruses will be used to transfer several new genes into beta cells to improve their resistance to immune attack, so that they can be transplanted into people with established diabetes without the need for potentially toxic drugs that suppress the immune system overall. The integrated research of the team is helping to provide a sound, rational base for the eventual prevention and cure of type 1 diabetes.Read moreRead less
Genetic And Bioinformatic Analysis Of Complex Human Diseases
Funder
National Health and Medical Research Council
Funding Amount
$8,752,567.00
Summary
Some human diseases are common in families; examples include prostate cancer, blood cancers, epilepsy and diabetes. Therefore, close relatives of individuals with a disease have an increased risk of being affected by this disease, implying a genetic basis. Finding the cause of these diseases is difficult, we will be developing novel approaches to the identification of genes responsible for these diseases. This is the first step towards the development of treatments for affected individuals.
Neourobiology Of Human Epilepsy: Genes, Cellular Mechanisms,network And Whole Brain
Funder
National Health and Medical Research Council
Funding Amount
$17,652,824.00
Summary
The team is comprised of neurologists, molecular geneticists, physiologists and brain imaging specialists and leads the world in the discovery of the genetic causes of epilepsy. They will continue to identify genes underlying epilepsy and study how genetic variations result in development of seizures. Advanced brain imaging will be used to understand the effects of genetic variation on brain structure and function. This study may lead to new diagnostic methods and treatments for epilepsy.
Molecular Determinants Of Risk, Progression And Treatement Response In Melenoma
Funder
National Health and Medical Research Council
Funding Amount
$12,947,193.00
Summary
Melanoma is a major Australian health problem. It is the third most common cancer in men and women and has a disproportionately heavy impact on productive years of life because it is the common cause of cancer death in younger adults. The investigators are all associated with the Melanoma Institute Australia, incorporating the Sydney Melanoma Unit (SMU). MIA is the world’s largest clinical service dedicated to the treatment of melanoma, treating >1500 new melanoma patients annually and mainta ....Melanoma is a major Australian health problem. It is the third most common cancer in men and women and has a disproportionately heavy impact on productive years of life because it is the common cause of cancer death in younger adults. The investigators are all associated with the Melanoma Institute Australia, incorporating the Sydney Melanoma Unit (SMU). MIA is the world’s largest clinical service dedicated to the treatment of melanoma, treating >1500 new melanoma patients annually and maintains a repository of clinical data on melanoma and a large melanoma tissue bank. The Program has also recruited large numbers of people from the community, as well as people with a strong family history of melanoma, in order to study its causes. It aims to utilise these internationally-recognised resources to develop a scientific basis for 1) improved management of individuals at high risk for development and progression of melanoma, and 2) improved treatment of patients with early and disseminated melanoma, in an era of rapid change in the prospects of successfully treating this dangerous cancer. The Program will do this by consolidating and extending its existing collaborative research, supported by NHMRC since 2006.Read moreRead less
To understand the genetic basis of two of the most important cancers in women, breast and ovarian cancer. The team has already identified one gene that confers a very high risk of breast cancer and may account for a large proportion of 'familial' breast cancer. Their aim is to identify additional predisposition genes and to determine their normal function in the cell, as well as the way in which they contribute to the development of cancer
Molecular Determinants Of Risk, Progression And Treatment Response In Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$8,381,820.00
Summary
Melanoma is a major Australian health problem. NSW figures for 2002 show it to be the second most common cancer in men and women. It has a disproportionately heavy impact on productive years of the life of young Australians because it is the commonest cancer in those aged 15-45 years. The investigators are all associated with the Sydney Melanoma Unit (SMU), the world�s largest clinical service dedicated to the treatment of melanoma, treating >1200 new melanoma patients annually. We have also ....Melanoma is a major Australian health problem. NSW figures for 2002 show it to be the second most common cancer in men and women. It has a disproportionately heavy impact on productive years of the life of young Australians because it is the commonest cancer in those aged 15-45 years. The investigators are all associated with the Sydney Melanoma Unit (SMU), the world�s largest clinical service dedicated to the treatment of melanoma, treating >1200 new melanoma patients annually. We have also recruited large cohorts of individuals with high susceptibility to melanoma, both familial and population-based, throughout southeastern Australia. We aim to utilise these unique, internationally-recognised resources to develop a scientific basis for 1) improved management of individuals at high risk for development and progression of melanoma, and 2) improved treatment of patients with early and disseminated melanoma. We will base this on consolidation of existing collaborative research into molecular predictors of risk, progression and treatment response in melanoma.Read moreRead less
Molecular Regulation Of Blood Cell Production And Function
Funder
National Health and Medical Research Council
Funding Amount
$18,333,174.00
Summary
The blood-forming system is an intricately controlled balance of cell proliferation, maturation and functional activity that is essential for oxygen transport throughout the body, blood clotting, and effective immune responses. Defining the genes and molecules that orchestrate blood cell production and function is crucial, not only for understanding the role of blood in health, but for establishing the bases of blood cell disorders such as autoimmunity and leukaemia, and for devising new clinica ....The blood-forming system is an intricately controlled balance of cell proliferation, maturation and functional activity that is essential for oxygen transport throughout the body, blood clotting, and effective immune responses. Defining the genes and molecules that orchestrate blood cell production and function is crucial, not only for understanding the role of blood in health, but for establishing the bases of blood cell disorders such as autoimmunity and leukaemia, and for devising new clinical strategies for fighting these lethal diseases. This program is conducted by a large, established team of investigators that have made world-class contributions to understanding blood cell formation and function for more than 30 years. Their work established the modern era of molecular haematology via discovery and analysis of blood cell hormones (colony-stimulating factors or CSFs), their receptors and intracellular mediators, which resulted in development of treatments for millions of cancer patients. The program is a multidisciplinary, team approach to fundamental biological questions with a focus on potential clinical and commercial outcomes involving collaborations with clinical medicine and the pharmaceutical industry. Research will focus on meshing novel genetic approaches in mice with translation studies in humans to identify new validated targets for therapeutic intervention in blood cell diseases, as well as building on the team s expertise in cytokine action with emphasis on the actions of the suppressor of cytokine signalling (SOCS) molecules, a key family of proteins that controls cytokine actions.Read moreRead less