Investigating the atomic structure of an immune cell inhibitory receptor. T cells play a key role in the adaptive immune system, whose reactivity must be controlled to prevent aberrant reactivity. Central to the function of T cells is the T cell antigen receptor, and a host of co-stimulatory molecules, co-receptors and inhibitory receptors. This proposal, in partnership with Immutep Ltd, aims to gain a basic understanding of the structure and function of a key inhibitory receptor found on T cel ....Investigating the atomic structure of an immune cell inhibitory receptor. T cells play a key role in the adaptive immune system, whose reactivity must be controlled to prevent aberrant reactivity. Central to the function of T cells is the T cell antigen receptor, and a host of co-stimulatory molecules, co-receptors and inhibitory receptors. This proposal, in partnership with Immutep Ltd, aims to gain a basic understanding of the structure and function of a key inhibitory receptor found on T cells, termed the Lymphocyte activation gene-3 (LAG-3). The proposal utilises a combination of cellular immunology and structural biology to gain insight into the form and function of the LAG-3 molecule. Ultimately this fundamental knowledge can be used by the biotechnology industry.Read moreRead less
I am a developmental cell biologist and molecular geneticist focusing on mechanisms controlling cell proliferation and modelling the development of cancer in the vinegar fly, Drosophila.
The Australian Proteomics Computational Facility (APCF)
Funder
National Health and Medical Research Council
Funding Amount
$2,509,000.00
Summary
In recent years, Australia has invested in the equipment capable of identifying proteins important in health and medicine. This sophisticated equipment requires high capacity computing support. The Australian Proteomics Computational Facility will establish a single advanced computing cluster accessible to scientists at proteomics centres all over the country. This integrated approach to proteomics computing and the sharing of databases will put Australia at the forefront of the world�s efforts ....In recent years, Australia has invested in the equipment capable of identifying proteins important in health and medicine. This sophisticated equipment requires high capacity computing support. The Australian Proteomics Computational Facility will establish a single advanced computing cluster accessible to scientists at proteomics centres all over the country. This integrated approach to proteomics computing and the sharing of databases will put Australia at the forefront of the world�s efforts to identify the proteins associated with the early detection of our major diseasesRead moreRead less
The roles of novel pathways in the activation and regulation of the adaptive immune response in health and disease. The immune system is designed to protect us against infection and vaccines exploit this with great success in preventing many infections. However, the immune system can also 'fail' and attack the body in a process called autoimmunity e.g. destroying joints in rheumatoid arthritis. This proposal will define how white blood cells work to make better vaccines against infection and ho ....The roles of novel pathways in the activation and regulation of the adaptive immune response in health and disease. The immune system is designed to protect us against infection and vaccines exploit this with great success in preventing many infections. However, the immune system can also 'fail' and attack the body in a process called autoimmunity e.g. destroying joints in rheumatoid arthritis. This proposal will define how white blood cells work to make better vaccines against infection and how these same immune cells can malfunction to create autoimmune diseases like Crohn's disease.Read moreRead less
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
The insulin-like growth factor system is involved in promoting cancer growth and survival against treatment with chemotherapy. Insulin-like growth factors-I and -II act via cell surface receptors (IGF-1R). Much effort has been applied to blocking the action of insulin-like growth factors via IGF-1R. However, recently a second mechanism has been identified by which the insulin-like growth factors are involved in cancer. Insulin-like growth factor-II can also promote cancer growth and survival via ....The insulin-like growth factor system is involved in promoting cancer growth and survival against treatment with chemotherapy. Insulin-like growth factors-I and -II act via cell surface receptors (IGF-1R). Much effort has been applied to blocking the action of insulin-like growth factors via IGF-1R. However, recently a second mechanism has been identified by which the insulin-like growth factors are involved in cancer. Insulin-like growth factor-II can also promote cancer growth and survival via an alternative form of the insulin receptor. We will join with our international collaborator to bring together a team of biochemists and protein structural biologists who are world leaders in understanding protein interactions in the insulin and insulin-like growth factor systems. As relatively little is known about this alternate pathway we propose to define the mechanism of binding of insulin-like growth factor-II to the alternate insulin receptor isoform. Using a combination of well-established and novel techniques we will map the interaction. This knowledge will allow design of specific inhibitors to block the action of insulin-like growth factor-II in promotion of cancer cell growth and survival without disruption of the metabolic actions of the insulin receptor.Read moreRead less
Investigating gamma/delta T cell receptor recognition determinants. The immune system has evolved to protect hosts from pathogens. T cells are a critical component of the immune system that can recognise infected host cells. However, there remains many facets of T cell function that we do not understand. This project aims to investigate a major aspect of T cell immunity that is poorly understood, namely, gamma/delta T cell immunity. Specifically, using a multi-disciplinary approach, the anticip ....Investigating gamma/delta T cell receptor recognition determinants. The immune system has evolved to protect hosts from pathogens. T cells are a critical component of the immune system that can recognise infected host cells. However, there remains many facets of T cell function that we do not understand. This project aims to investigate a major aspect of T cell immunity that is poorly understood, namely, gamma/delta T cell immunity. Specifically, using a multi-disciplinary approach, the anticipated outcome of the project is to unearth the molecular recognition determinants of gamma/delta T cells. The intended outcome is to provide basic fundamental insights and conceptual advances into a poorly understood, but crucial, component of the immune system. Read moreRead less
Deregulation Of Ribosome Signalling, Synthesis And Function During Malignant Transformation.
Funder
National Health and Medical Research Council
Funding Amount
$522,773.00
Summary
A major feature of tumour progression is accelerated cell growth and protein synthesis. Moreover, increased synthesis of ribosomes (the protein synthetic machinery) is associated with malignancy suggesting that it may play a causal role in cancer formation. In support of this, specific inhibitors of both ribosome biogenesis and function are extremely effective in inhibiting the growth of some tumours. This study will examine the mechanisms of deregulation of ribosome biogenesis and function duri ....A major feature of tumour progression is accelerated cell growth and protein synthesis. Moreover, increased synthesis of ribosomes (the protein synthetic machinery) is associated with malignancy suggesting that it may play a causal role in cancer formation. In support of this, specific inhibitors of both ribosome biogenesis and function are extremely effective in inhibiting the growth of some tumours. This study will examine the mechanisms of deregulation of ribosome biogenesis and function during cancer formation and assess for the first time whether aberrant regulation of ribosome biogenesis and function directly contributes to the initiation and-or progression of cancer.Read moreRead less