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
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
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE160100097
Funder
Australian Research Council
Funding Amount
$675,000.00
Summary
An Automated Protein Nano-Crystallisation Facility. An automated protein nano-crystallisation facility:
The project aims to establish a high throughput protein nanocrystallisation and imaging facility for protein crystallography. Protein crystallography is an important field of biological research, however there are many proteins, such as integral membrane proteins and transient molecular complexes that are more challenging to crystallise. The facility aims to use state-of-the-art imaging and c ....An Automated Protein Nano-Crystallisation Facility. An automated protein nano-crystallisation facility:
The project aims to establish a high throughput protein nanocrystallisation and imaging facility for protein crystallography. Protein crystallography is an important field of biological research, however there are many proteins, such as integral membrane proteins and transient molecular complexes that are more challenging to crystallise. The facility aims to use state-of-the-art imaging and crystallisation techniques, including second order nonlinear imaging of chiral crystals (SONICC) imaging and lipid cubic phase approaches, to enable structural studies to be undertaken on challenging proteins. This information is often used for the rational development of therapeutics. The facility would support cutting-edge biological research In Australia.Read moreRead less
A novel axis of cooperation between innate and adaptive immunity. The project aims to understand how two molecular components of the immune system, Complement and MHC, cooperate to protect the host. Further, these two molecules mediate trogocytosis, a little-studied form of intercellular communication, between two major immune cell types: dendritic cells and B cells. The project will be multidisciplinary, applying high-end microscopy, biochemistry, cell biology and immunology techniques. Person ....A novel axis of cooperation between innate and adaptive immunity. The project aims to understand how two molecular components of the immune system, Complement and MHC, cooperate to protect the host. Further, these two molecules mediate trogocytosis, a little-studied form of intercellular communication, between two major immune cell types: dendritic cells and B cells. The project will be multidisciplinary, applying high-end microscopy, biochemistry, cell biology and immunology techniques. Personnel will be trained in cutting-edge techniques. The project will expand knowledge on basic immunology and cell-cell cooperation. It will generate intellectual property for the biotechnology sector to develop new commercial products that might improve the health of humans and also animals of economic importance.Read moreRead less
The development of tyrosine kinase inhibitors for the treatment of inflammation and malignant disease. Through the combination of expertise from the Industry partner and the Hume group this project aims to develop specific inhibitors of the CSF-1 receptor protein tyrosine kinase in order to demonstrate their efficacy as modulators of CSF-1 dependent macrophage and tumour cell function in vitro. The expected outcome will be a lead set of targets which can be further assessed for therapeutic pote ....The development of tyrosine kinase inhibitors for the treatment of inflammation and malignant disease. Through the combination of expertise from the Industry partner and the Hume group this project aims to develop specific inhibitors of the CSF-1 receptor protein tyrosine kinase in order to demonstrate their efficacy as modulators of CSF-1 dependent macrophage and tumour cell function in vitro. The expected outcome will be a lead set of targets which can be further assessed for therapeutic potential in clinical trials.Read moreRead less
A novel link between metabolism and host defence. This project aims to delineate how a protein modification that consists of the addition of a small sugar to cellular proteins, known as O-GlcNAcylation, provides a link between metabolism and complex cell functions. The model for these studies is a cell type of the immune system known as dendritic cells. Upon encountering pathogens these cells undergo metabolic changes that increase the rate of O-GlcNAcylation of proteins involved in immune respo ....A novel link between metabolism and host defence. This project aims to delineate how a protein modification that consists of the addition of a small sugar to cellular proteins, known as O-GlcNAcylation, provides a link between metabolism and complex cell functions. The model for these studies is a cell type of the immune system known as dendritic cells. Upon encountering pathogens these cells undergo metabolic changes that increase the rate of O-GlcNAcylation of proteins involved in immune responses, altering their function. This project will study how O-GlcNAcylation works and is regulated. The project expects to develop new technology and provide high-level training, increasing the competitiveness of the strategic biotechnology sector in AustraliaRead moreRead less
The role of the protease inhibitor Serpinb9 in antigen cross-presentation by dendritic cells. This project will provide fundamental new insights into antigen cross-presentation, a crucial facet of the immune system's response to viral infection or neoplastic cells. It will also provide a basis for future studies into mechanisms of immune tolerance and enhance our understanding of autoimmune disease.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0882913
Funder
Australian Research Council
Funding Amount
$300,000.00
Summary
Mass spectrometry facility for the quantitation and analysis of post-translationally modified peptides. This proposal will address a gap in our mass spectrometry capabilities and aid in our understanding of the cellular immune response and investigate the chemical diversity of the targets of immunity. This proposal has broad implications in the basic immunology of antigen presentation, in biomarker discovery as well as in the design of new vaccines in infectious disease and cancer and the develo ....Mass spectrometry facility for the quantitation and analysis of post-translationally modified peptides. This proposal will address a gap in our mass spectrometry capabilities and aid in our understanding of the cellular immune response and investigate the chemical diversity of the targets of immunity. This proposal has broad implications in the basic immunology of antigen presentation, in biomarker discovery as well as in the design of new vaccines in infectious disease and cancer and the development of therapies for autoimmune diseases. In addition to these key scientific outcomes this project will also facilitate the training of several new personnel in a skill area for which there is a critical shortage (mass spectrometry) and promote cross-disciplinary skills (immunology, biochemistry, proteomics).Read moreRead less