Muscarinic Receptor Signalling, Transglutaminase And Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$518,210.00
Summary
Diabetes is a major and increasing cuase of death and disability in our society. This studies aims to understand the cellular and molecular mechaisms controlling insulin secretion from the pancreas, since defects in this secretion are involved in causing diabetes. The proposed studies are of relevance to both juvenile and adult-onset diabetes, and may lead to new treatment modalities, as well as potentially being relevant to the use of pencreatic islet cell transplantation in the treatment of di ....Diabetes is a major and increasing cuase of death and disability in our society. This studies aims to understand the cellular and molecular mechaisms controlling insulin secretion from the pancreas, since defects in this secretion are involved in causing diabetes. The proposed studies are of relevance to both juvenile and adult-onset diabetes, and may lead to new treatment modalities, as well as potentially being relevant to the use of pencreatic islet cell transplantation in the treatment of diabetes.Read moreRead less
Integrin-growth Factor Interactions In The Development Of Airway Wall Remodelling
Funder
National Health and Medical Research Council
Funding Amount
$405,300.00
Summary
Asthma is a clinically and socio-economically important disease with prevalence in the Australian population of approximately 13% for adults and approaching 25% for children. Currently, glucocorticoids (GCS) are first line prophylactic therapy for the disease. Despite a wide diversity of precipitating factors, the mechanisms underlying its pathogenesis remain unclear. A marked thickening of the airway wall bought about by excessive deposition of extracellular matrix is a prominent pathological f ....Asthma is a clinically and socio-economically important disease with prevalence in the Australian population of approximately 13% for adults and approaching 25% for children. Currently, glucocorticoids (GCS) are first line prophylactic therapy for the disease. Despite a wide diversity of precipitating factors, the mechanisms underlying its pathogenesis remain unclear. A marked thickening of the airway wall bought about by excessive deposition of extracellular matrix is a prominent pathological feature but why this occurs and how it can be prevented is equally unclear. Recent studies have suggested that interactions between cells and the extracellular matrix influence the airways response to inflammation and modulate the effectiveness of currently available therapies. Indeed, there is mounting evidence to suggest that GCS fail to modulate and indeed in some cases even contribute to structural changes in the remodeled airway wall. The aim of this study is to assess the mechanisms by which cells and the extracellular matrix interact to promote remodelling of the airway wall and to determine whether this association influences the responsiveness to traditional asthma therapies.Read moreRead less
Investigate The Role Of Platelet Von Willebrand Factor In Initiating Platelet Aggregation Under Flow
Funder
National Health and Medical Research Council
Funding Amount
$307,165.00
Summary
Platelets are small specialised blood cells that are essential for normal blood clotting and repair of damaged blood vessels following injury. We are studying the processes that enable platelets to stick to each other and to other cells to form a stable blood clot at the site of injury. The same processes, unchecked, are involved in the formation of harmful blood clots in the bloodstream that may block blood vessels in the heart or brain and result in a heart attack or stroke. Platelets stick to ....Platelets are small specialised blood cells that are essential for normal blood clotting and repair of damaged blood vessels following injury. We are studying the processes that enable platelets to stick to each other and to other cells to form a stable blood clot at the site of injury. The same processes, unchecked, are involved in the formation of harmful blood clots in the bloodstream that may block blood vessels in the heart or brain and result in a heart attack or stroke. Platelets stick to the blood vessel wall through specialised adhesive proteins. These adhesion proteins are stored within the platelet and expressed on the cell surface when the platelets stick to the blood vessel wall. In conditions such as Gray Platelet Syndrome, the platelets are unable to store adhesion receptors, resulting in impaired blood clot formation. A clearer understanding of how platelets stick to the blood vessel wall will not only increase our knowledge of blood clot formation in health and disease, but also with the potential development of new therapies for the prevention of heart disease and stroke.Read moreRead less
Gene Expression Changes Induced Upon Beta3 Integrin Expression In Human Melanoma Metastasis
Funder
National Health and Medical Research Council
Funding Amount
$199,413.00
Summary
Diagnostic and prognostic markers for metastatic melanoma are essential to better understand the development of this cancer. One of the most effective markers so far found to correlate with invasiveness of tumour cells, and hence lethality of melanoma, is the Beta3 integrin molecule. When this protein is expressed on the surface of early stage melanoma cells, that in themselves are not able to form metastatic tumours, they convey upon the cells the ability to proceed from growing on the surface ....Diagnostic and prognostic markers for metastatic melanoma are essential to better understand the development of this cancer. One of the most effective markers so far found to correlate with invasiveness of tumour cells, and hence lethality of melanoma, is the Beta3 integrin molecule. When this protein is expressed on the surface of early stage melanoma cells, that in themselves are not able to form metastatic tumours, they convey upon the cells the ability to proceed from growing on the surface of the skin (radial growth phase) to allowing them to invade the skin (vertical growth phase). It is not clear how expression of Beta 3 allows this change in growth state to occur and this research program is designed to test if Beta 3 is the direct cause of gene expression changes mediating the metastatic transformation. To provide insight into the genetic changes induced in melanoma cells expressing the Beta3 protein a screen for genes that are either activated or repressed in the presence of Beta3 will be performed. Non-metastatic melanoma cells will be transduced with the Beta 3 gene and a molecular technique applied to these cells that can identify genetic differences which will allow the cloning of differentially expressed genes. The gene fragments that are identified will first provide clues as to what the genes are that maybe switched on or off to allow the tumour to grow beneath the skin. They will also form the basis of a Ometastatic melanoma gene panelO that can be tested for its diagnostic value of tumours. The utility and reproducibility of the gene panel will be confirmed by testing melanoma cell lines and tumour tissue. These experiments should lead to better diagnosis of metastatic melanoma and also possible new avenues to develop therapies for the disease.Read moreRead less