Proteases, Their Inhibitors And Receptors In Degenerative Disease
Funder
National Health and Medical Research Council
Funding Amount
$5,843,388.00
Summary
Many of the themes of this program are aimed at understanding the molecular basis of several important degenerative diseases that in particular affect the ageing population. These include osteoporosis, arthritis, periodontal disease, wasting diseases of muscle and inherited disorders such as antitrypsin deficiency. The five CI’s on this application have formed a collaborative network since 1996. Dr Whisstock is a bioinformatician and structural biologist with a research focus on the serpin super ....Many of the themes of this program are aimed at understanding the molecular basis of several important degenerative diseases that in particular affect the ageing population. These include osteoporosis, arthritis, periodontal disease, wasting diseases of muscle and inherited disorders such as antitrypsin deficiency. The five CI’s on this application have formed a collaborative network since 1996. Dr Whisstock is a bioinformatician and structural biologist with a research focus on the serpin superfamily of protease inhibitors and their protease partners. He is currently the scientific director of the Victorian Bioinformatics Consortium and an NHMRC Senior Research Fellow. Dr Bird is an NHMRC Senior Research Fellow who discovered the intracellular branch of the serpin superfamily and formulated the hypothesis that describes their function. A-Prof Mackie is a world expert in the field of musculoskeletal biology and pathology. Dr Bottomley is a Senior Logan Fellow and RD Wright Fellow whose research focuses upon how proteins misfold and lead to disease. Dr Pike is an enzymologist whose research area encompasses a wide range of bacterial and mammalian proteases involved in the pathology of human disease. Each individual in this team brings different skills which makes this a very important and powerful collaboration. The research is extensive and involves protein folding, enzyme kinetics, molecular modelling, structural biology, bioinformatics, cell biology and pathology, enzyme kinetics and drug design. Collectively the CI’s have a total of 154 papers since 1998, of which a third include two or more of the CI’s as co-authors. Currently the team holds over >$5 million in grant funding. The team is augmented by four P.I.s: Dr Buckle is a talented structural biologist; Dr Scott is a molecular cell biologist who holds an NHMRC CJ Martin Fellow; Dr Garcia de la Banda is a computer scientist based at Monash and Dr Grigoryev is a world expert in chromatin condensation based at Penn State University (USA).Read moreRead less
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
Type 1 diabetes (T1D) is a major chronic disease affecting over 100,000 Australians. Its treatment and complications impose a significant burden on affected individuals and their families and on the health system. T1D occurs when the immune system attacks insulin-producing cells in the islet cells of the pancreas. The team has developed ways to identify at-risk people, defined immune and genetic causes of T1D and is undertaking prevention trials and Australia's first islet transplant program. Th ....Type 1 diabetes (T1D) is a major chronic disease affecting over 100,000 Australians. Its treatment and complications impose a significant burden on affected individuals and their families and on the health system. T1D occurs when the immune system attacks insulin-producing cells in the islet cells of the pancreas. The team has developed ways to identify at-risk people, defined immune and genetic causes of T1D and is undertaking prevention trials and Australia's first islet transplant program. Their multidisciplinary research is taking us closer to the prevention and cure of T1D.Read moreRead less
The Biology & Therapeutic Manipulation Of Lymphatic Vessels In Cancer & Lymphedema
Funder
National Health and Medical Research Council
Funding Amount
$2,589,101.00
Summary
This proposal brings together a team of researchers from diverse backgrounds who have already made important discoveries about the molecular control of the lymphatic system in normal physiology and cancer. The lymphatic vasculature consists of a network of vessels in organs and tissues that is critical for the regulation of tissue fluid volume and immune function. The lymphatics are also important for the metastatic spread of cancer, as they provide a route by which tumour cells spread to distan ....This proposal brings together a team of researchers from diverse backgrounds who have already made important discoveries about the molecular control of the lymphatic system in normal physiology and cancer. The lymphatic vasculature consists of a network of vessels in organs and tissues that is critical for the regulation of tissue fluid volume and immune function. The lymphatics are also important for the metastatic spread of cancer, as they provide a route by which tumour cells spread to distant sites in the body, and for lymphedema, a condition in which lymphatic dysfunction leads to swelling of tissues. This program will explore the molecular mechanisms that control the growth and differentiation of the lymphatic vessels. It will greatly enhance our understanding of lymphatic vessel growth (lymphangiogenesis) and generate a range of reagents for stimulating or inhibiting this process. These reagents will be tested in animal models for their capacity to modulate lymphatic function in the context of cancer and lymphedema.Read moreRead less