Control Of CD4 Function By Disulphide-Bond Switching
Funder
National Health and Medical Research Council
Funding Amount
$252,761.00
Summary
CD4 is a cell-surface protein that has two functions in the human body, a good one and a bad one. Its good function is as a checkpoint for development of the immune system and for response of the immune system to infection. It helps immune cells known as T cells to recognize and dispose of a foreign particle in the body. Its bad function is that it is one of two proteins that enable the HIV virus to enter and destroy immune cells. The HIV virus binds to CD4 on immune cells, which leads to fusion ....CD4 is a cell-surface protein that has two functions in the human body, a good one and a bad one. Its good function is as a checkpoint for development of the immune system and for response of the immune system to infection. It helps immune cells known as T cells to recognize and dispose of a foreign particle in the body. Its bad function is that it is one of two proteins that enable the HIV virus to enter and destroy immune cells. The HIV virus binds to CD4 on immune cells, which leads to fusion of the viral and immune cell surfaces and entry of the virus into the cell. Once inside the immune cell the virus reproduces itself and goes on to kill more immune cells. AIDS results when too many immune cells are killed. We have discovered that CD4 exists in three different forms on the immune cell surface; an oxidized, reduced or dimeric form. These different forms result from a molecular switch we discovered in CD4. We have suggested that the good and bad functions of CD4 are mediated by different forms of CD4. The good function is mediated by dimeric CD4, while the bad function is mediated by reduced CD4. The purpose of this application is to test this hypothesis. If we are correct then our findings will have significant implications for our understanding of how the immune system responds to a foreign invader and how HIV-AIDS destroys the immune system. This knowledge could be used to develop drugs that suppress the immune system when required, such as in organ transplantation, and that fight HIV-AIDS.Read moreRead less
A Lineage Specific Pathway For Progression Of Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$485,746.00
Summary
Melanoma is an insidious cancer, and its incidence has increased dramatically over the past four decades. Melanoma has an almost universally poor prognosis once metastasis has occurred. There are currently no treatment regimens that have a significant impact on prolonging survival or decreasing mortality from metastatic melanoma. Our preliminary data has shown the importance of a factor found in normal melanocytes in control over expression of a separate factor required for invasion and metastas ....Melanoma is an insidious cancer, and its incidence has increased dramatically over the past four decades. Melanoma has an almost universally poor prognosis once metastasis has occurred. There are currently no treatment regimens that have a significant impact on prolonging survival or decreasing mortality from metastatic melanoma. Our preliminary data has shown the importance of a factor found in normal melanocytes in control over expression of a separate factor required for invasion and metastasis of melanoma. These markers could serve as an important diagnostic marker for melanoma. Further, they may be suitable drug targets for the prevention and treatment of metastatic melanoma, and will advance our understanding of how melanoma spreads.Read moreRead less
The Role Of MIC-1 In The Promotion And Progression Of Skin Squamous Cell Carcinoma.
Funder
National Health and Medical Research Council
Funding Amount
$237,258.00
Summary
Skin cancers are the most common human tumours and the incidence is increasing. Ultra-violet (UV) light is the main factor in the formation of skin cancer. This project will find how a gene product (MIC-1) induced by solar UV affects the skin, and why we see it in skin cancers. This protein has other interesting properties that could bear directly on measuring sun exposure and understanding skin cancer. A processed form is released into the blood, where it could carry UV signals and be used in p ....Skin cancers are the most common human tumours and the incidence is increasing. Ultra-violet (UV) light is the main factor in the formation of skin cancer. This project will find how a gene product (MIC-1) induced by solar UV affects the skin, and why we see it in skin cancers. This protein has other interesting properties that could bear directly on measuring sun exposure and understanding skin cancer. A processed form is released into the blood, where it could carry UV signals and be used in population studies as a measure of sun exposure. It's also induced by certain cancer-promoting chemicals which resemble UV light in their immediate effects. A lot could therefore be learnt from this protein, and if we find that MIC-1 promotes the growth of normal and tumour cells in the skin after UV exposure, we can look for ways to stop this happening.Read moreRead less