Activated Protein C Utilises Protease Activated Receptors And Epidermal Growth Factor Receptor To Heal Wounds
Funder
National Health and Medical Research Council
Funding Amount
$436,882.00
Summary
Chronic leg ulcers are a major burden to the individual sufferer and to the health system. We have discovered that activated protein C (APC) potently stimulates wound healing in the laboratory and now have exciting positive results from a small pilot clinical trial showing that applying APC solution to leg ulcers also helps healing in patients. This study plans to discover how APC works at the molecular level.
Regulation Of Stat1 Activity Levels: Abnormalities In Human Melanoma Cells Resistant To Interferon.
Funder
National Health and Medical Research Council
Funding Amount
$227,036.00
Summary
Melanoma and its treatment continues to be an important health concern in Australia. The interferons comprise an elaborate system of natural substances produced in the body, one of whose functions is to prevent cancer cells from developing. The interferons have been widely used to treat human diseases including viral infections and cancers like malignant melanoma. However, results of recent trials have cast doubt on its effectiveness. We have found that advanced stage melanoma cells resist the d ....Melanoma and its treatment continues to be an important health concern in Australia. The interferons comprise an elaborate system of natural substances produced in the body, one of whose functions is to prevent cancer cells from developing. The interferons have been widely used to treat human diseases including viral infections and cancers like malignant melanoma. However, results of recent trials have cast doubt on its effectiveness. We have found that advanced stage melanoma cells resist the direct anti-cancer effects of interferons because they have abnormalities in their ability to respond to interferon. We have made good progress in understanding why the melanoma cells do not respond to the interferons. In particular they show a deficiency in the activity of protein, Stat1, required to send the interferon signal inside the cells. The current proposal will allow us to gain a greater understanding of the processes inside cancer cells regulating Stat1 activity and the reasons for its abnormality in interferon resistant cancer cells. This study will help establish an assay to predict which cancer patients will respond to interferon therapy, saving pateints from unecessary discomfort and costs. It will also have a broad significance to many human diseases where abnormalities in interferon signaling occur and will help to bring about ways to produce the necessary changes in cell properties to overcome the abnormalites, restore the responses and improve the application of interferons to treat melanoma and perhaps other human diseases as well.Read moreRead less
The Role Of Keratin End-domains In Filament Biology
Funder
National Health and Medical Research Council
Funding Amount
$139,235.00
Summary
The skin is the largest organ in the body and is the main interface between the organism and the external environment. It protects us from UV radiation, microbial invasion and chemical attack. It is able to repair itself and in fact, is continually renewing itself. In this study, we propose to examine the biology of keratins and the filament networks they form. Keratins are the most abundant proteins present in the epidermis, the outer layer of the skin. Keratins form a cellular skeleton that re ....The skin is the largest organ in the body and is the main interface between the organism and the external environment. It protects us from UV radiation, microbial invasion and chemical attack. It is able to repair itself and in fact, is continually renewing itself. In this study, we propose to examine the biology of keratins and the filament networks they form. Keratins are the most abundant proteins present in the epidermis, the outer layer of the skin. Keratins form a cellular skeleton that reinforces skin cells to help them withstand mechanical trauma. Mutations in these proteins result in a much weaker skeleton and ultimately in disease. We will examine how the keratin building blocks are transported around the cell to where they are needed. We will also determine the effect of mutations in this transport process on the biology of the cell. These studies may provide important clues into certain inherited skin disorders.Read moreRead less
Interactions of Insulin-like Growth Factors and their Binding Proteins with Vitronectin: a structural basis for antagonist design and development. Tissue Therapies Ltd has shown that a patented combination of three biosynthetic molecules, VitroGroR, can promote tissue repair effectively. This project will use biophysical and biochemical techniques to investigate precisely how these molecules interact, and hence provide a rational basis for future developments and improvements of this exciting n ....Interactions of Insulin-like Growth Factors and their Binding Proteins with Vitronectin: a structural basis for antagonist design and development. Tissue Therapies Ltd has shown that a patented combination of three biosynthetic molecules, VitroGroR, can promote tissue repair effectively. This project will use biophysical and biochemical techniques to investigate precisely how these molecules interact, and hence provide a rational basis for future developments and improvements of this exciting new therapeutic strategy.
Conversely, this information would also facilitate the development of antagonists to VitroGroR complexes would provide novel opportunities to treat diseases such as cancer and atherosclerosis that involve excessive production of its component molecules.Read moreRead less
Raman spectroscopy and imaging of natural and synthetic melanins. The national benefit of this research lies in three main areas. First, this research could lead to a non-invasive diagnostic for melanoma. Second, it could reveal stronger connections between melanin and melanoma development than previously believed and thus inspire possible methods of treatment or prevention of melanoma. Given Australia's high incidence of melanoma, these could have an enormous impact on our health care system. T ....Raman spectroscopy and imaging of natural and synthetic melanins. The national benefit of this research lies in three main areas. First, this research could lead to a non-invasive diagnostic for melanoma. Second, it could reveal stronger connections between melanin and melanoma development than previously believed and thus inspire possible methods of treatment or prevention of melanoma. Given Australia's high incidence of melanoma, these could have an enormous impact on our health care system. Third, it will increase our understanding of the melanin pigment and further establish Australia as a leader in this field. Given the links between melanin and Parkinson's Disease and immune response, this understanding could have greater impact on health care than simply melanoma.Read moreRead less
Mechanisms Defining Microfibril And Elastic Fibre Assembly, Structure And Function.
Funder
National Health and Medical Research Council
Funding Amount
$619,721.00
Summary
Elastic fibres are important in tissues such as arteries, lung and skin where they provide elasticity. Disruption of their normal structure and function is a major aspect of common diseases such as atherosclerosis, aneurisms, heart valve prolapse, emphysema, and the congenital disorder, Marfan syndrome. Elastic fibres consist of a core of the protein elastin surrounded by 12 nm glycoprotein microfibrils. During development the microfibrils always appear before the elastin and seem to act as a sc ....Elastic fibres are important in tissues such as arteries, lung and skin where they provide elasticity. Disruption of their normal structure and function is a major aspect of common diseases such as atherosclerosis, aneurisms, heart valve prolapse, emphysema, and the congenital disorder, Marfan syndrome. Elastic fibres consist of a core of the protein elastin surrounded by 12 nm glycoprotein microfibrils. During development the microfibrils always appear before the elastin and seem to act as a scaffold for the deposition of its precursor, tropoelastin. However knowledge of the role of each glycoprotein in the assembly, architecture, function and cell biology of microfibrils and elastic fibres is still very limited. Our laboratory has identified, cloned and characterised several microfibrillar proteins and we are uniquely placed to exploit our expertise and unique range of research tools to elucidate the mechanisms involved in the above processes. The Specific Aims are to determine a) the roles of individual components and associated proteins in microfibril and elastic fibre biology b) the architecture of microfibrils and the relationship of their structural heterogeneity to function during tissue development, c) the mechanisms responsible for microfibril and elastic fibre assembly, and other microfibril interactions with the cell surface, d) the gene regulatory mechanisms controlling expression of individual microfibrillar proteins and e) causative mutations of non-fibrillin genes in Marfan-like congenital disorders. The research will greatly increase our fundamental knowledge of the factors controlling the complex molecular mechanisms involved in microfibril assembly and elastic fibre formation, including the roles of individual microfibril-associated proteins, cell surface receptors, cellular processing, and gene regulation of these processes during normal development, which is essential before the full role of elastic fibres in major diseases can be understood.Read moreRead less
The role of palmitoylation in hair follicle and epidermal stem cell biology. A proteins activity can be shaped by sugar, phosphate and lipid modifications. This proposal will investigate the effects of the lipid modification called palmitoylation, about which we know very little. Our preliminary experiments suggest that palmitoylation is crucial for normal skin biology. We will explore its effects on the biology of the proteins which are modified, the cells in which they are found and the tis ....The role of palmitoylation in hair follicle and epidermal stem cell biology. A proteins activity can be shaped by sugar, phosphate and lipid modifications. This proposal will investigate the effects of the lipid modification called palmitoylation, about which we know very little. Our preliminary experiments suggest that palmitoylation is crucial for normal skin biology. We will explore its effects on the biology of the proteins which are modified, the cells in which they are found and the tissues in which they reside. Understanding more about these modifications will help us to learn more about the biology of our skin and will help us to understand diseases which affect our largest organ.Read moreRead less