Investigation of the fundamental roles of class Ib MHC (major histocompatibility complex) molecules in immunity. The proposed research program, using laboratory-based and synchrotron-based radiation, will provide insight into the roles of a poorly understood class of immune molecules. This will improve our understanding of the regulation of immunity, and the knowledge gained will increase Australia's international research profile.
Function and regulation of the Schlafen gene family: novel regulators of blood cell proliferation and function. The immediate outcomes of the proposed research will be in fundamental knowledge and understanding of important cellular and biological processes in which the Schlafen genes are involved. In particular, Schlafen genes are likely to play a role in inflammatory responses and in blood cell growth. These process clearly have relevance to a range of major human (and animal) diseases includ ....Function and regulation of the Schlafen gene family: novel regulators of blood cell proliferation and function. The immediate outcomes of the proposed research will be in fundamental knowledge and understanding of important cellular and biological processes in which the Schlafen genes are involved. In particular, Schlafen genes are likely to play a role in inflammatory responses and in blood cell growth. These process clearly have relevance to a range of major human (and animal) diseases including infectious disease, auto-immune disease and leukaemia, and thus a long-term outcome may be improved treatments for such disease. Read moreRead less
Investigation of a Phagocytic Synapse in the Uptake of Apoptotic Cells. Rapid clearance of cells that die by apoptosis is crucial for embryonic development, tissue turnover, and after inflammatory events. Specialised phagocytes engulf the apoptotic cell corpses in a way that minimises inflammation and prevents autoimmunity. Genetic studies have identified the key evolutionary receptors involved, but the molecular basis of this phagocytosis is still poorly understood. We have developed, and seek ....Investigation of a Phagocytic Synapse in the Uptake of Apoptotic Cells. Rapid clearance of cells that die by apoptosis is crucial for embryonic development, tissue turnover, and after inflammatory events. Specialised phagocytes engulf the apoptotic cell corpses in a way that minimises inflammation and prevents autoimmunity. Genetic studies have identified the key evolutionary receptors involved, but the molecular basis of this phagocytosis is still poorly understood. We have developed, and seek to establish, an integrated model that incorporates new findings to explain how the distinctive functions of specialised receptors can be orchestrated to achieve this function. A successful outcome to the project will provide new knowledge of value to human health.Read moreRead less
A structural investigation into the peptide-loading complex molecular machine. The proposed research program, using laboratory-based and synchrotron-based radiation, will provide fundamental insight into a process central to immunity, namely antigen presentation. Investigating the process of Antigen presentation is important, as it will further our understanding how a cell is "ear-marked" for being infected by viruses or bacteria. Such knowledge will increase Australia's international research ....A structural investigation into the peptide-loading complex molecular machine. The proposed research program, using laboratory-based and synchrotron-based radiation, will provide fundamental insight into a process central to immunity, namely antigen presentation. Investigating the process of Antigen presentation is important, as it will further our understanding how a cell is "ear-marked" for being infected by viruses or bacteria. Such knowledge will increase Australia's international research standing.Read moreRead less
Regulation of MHC-I and ICAM-1 by flavivirus, West Nile. This project investigates the intracellular signalling pathway responsible for the expression of genes which are critical to our immune response. We have demonstrated in a mouse model that high levels of expression of two of these genes in flavivirus encephalitis are associated with a survival advantage. We would expect this project to provide basic new information about the mechanisms of expression of these genes as well as information ab ....Regulation of MHC-I and ICAM-1 by flavivirus, West Nile. This project investigates the intracellular signalling pathway responsible for the expression of genes which are critical to our immune response. We have demonstrated in a mouse model that high levels of expression of two of these genes in flavivirus encephalitis are associated with a survival advantage. We would expect this project to provide basic new information about the mechanisms of expression of these genes as well as information about the interaction of this family of viruses, flavivirus with the host.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0989744
Funder
Australian Research Council
Funding Amount
$500,000.00
Summary
7-laser BD LSR-II and Cellomics ArrayScan VTi, to enhance capability and throughput for the NSW Advanced Cytometry Facility. The scientific advances that will be possible with the acquisition of these complementary cutting-edge instruments will enhance the research outputs of all investigators using it. Projects where investigation of either suspended or adherent live cells is used to elucidate basic life processes of eukaryotic cells across all species of animals, including the investigation of ....7-laser BD LSR-II and Cellomics ArrayScan VTi, to enhance capability and throughput for the NSW Advanced Cytometry Facility. The scientific advances that will be possible with the acquisition of these complementary cutting-edge instruments will enhance the research outputs of all investigators using it. Projects where investigation of either suspended or adherent live cells is used to elucidate basic life processes of eukaryotic cells across all species of animals, including the investigation of both normal and abnormal function, will be immeasurably enhanced by both the qualitative and quantitative statistical information about these processes that is generated by this instrumentation. This in turn will inform new approaches to improve and maintain the health of both humans and animals.Read moreRead less
The molecular basis of macropinocytosis in mammalian cells: the composition of endosome proteins and their function. Individual cells communicate with their immediate environment by the process of macropinocytosis, a process that involves the exchange of materials between the extracellular space and a specialised region of the cell termed endosomes. It is an important process in mammalian cells being essential to the correct functioning of many tissues. This project will advance understanding of ....The molecular basis of macropinocytosis in mammalian cells: the composition of endosome proteins and their function. Individual cells communicate with their immediate environment by the process of macropinocytosis, a process that involves the exchange of materials between the extracellular space and a specialised region of the cell termed endosomes. It is an important process in mammalian cells being essential to the correct functioning of many tissues. This project will advance understanding of macropinocytosis at a molecular level. The project is relevant to understanding the functioning of normal cells and the means by which some pathogens can enter cells and also understanding processes involved in tumour progression and metastasis.Read moreRead less
A novel role for the proteins Scribble & Dlg in the formation of cell protrusions and their effects on cell function. Dlg and Scribble are recently discovered proteins that are required during development, immune regulation, neural signalling and tumour suppression. Understanding how they work will enable the development of diagnostic and therapeutic tools that have the potential to influence an enormous range of diseases, from cancer to immunodeficiencies and autoimmune diseases. Researchers at ....A novel role for the proteins Scribble & Dlg in the formation of cell protrusions and their effects on cell function. Dlg and Scribble are recently discovered proteins that are required during development, immune regulation, neural signalling and tumour suppression. Understanding how they work will enable the development of diagnostic and therapeutic tools that have the potential to influence an enormous range of diseases, from cancer to immunodeficiencies and autoimmune diseases. Researchers at the PeterMac perform world-leading research into the biology of Scribble and Dlg, and their role in cancer biology and immune function. The mechanistic insight provided by this project will continue that tradition, and facilitate translation of our basic research into clinical applications in important disease areas.Read moreRead less
Lipid raft and cyotoskeleton organization: How membrane domains give cells direction. For a large number of cells in our body it is imperative that they are able to orientate themselves relative to their environment, sense direction and translate incoming signals. To do so it is hypothesised that lipids on the cell surface are redistributed to form specialized domains. An asymmetric distribution of membrane domains can provide cells with a front and rear end and can further concentrate and co-or ....Lipid raft and cyotoskeleton organization: How membrane domains give cells direction. For a large number of cells in our body it is imperative that they are able to orientate themselves relative to their environment, sense direction and translate incoming signals. To do so it is hypothesised that lipids on the cell surface are redistributed to form specialized domains. An asymmetric distribution of membrane domains can provide cells with a front and rear end and can further concentrate and co-ordinate signalling molecules to a specific site. The project will determine the role of lipid domain in stabilizing cell shape and their remodelling during cell migration, the digestion of foreign particles and the formation of cell-cell contacts.Read moreRead less
Determination of the mechanisms of immune system regulation of inflammation by the human protein, chaperonin 10. The aim of this project is to determine the mechanisms by which a human protein, chaperonin 10 (Cpn10), regulates the immune system and suppresses inflammation. When cells of the human immune system are challenged with lipopolysaccharide (LPS) (a product of bacterial infection), the pro-inflammatory cytokine TNF is released. Cpn10 has been shown to suppress production of TNF on chall ....Determination of the mechanisms of immune system regulation of inflammation by the human protein, chaperonin 10. The aim of this project is to determine the mechanisms by which a human protein, chaperonin 10 (Cpn10), regulates the immune system and suppresses inflammation. When cells of the human immune system are challenged with lipopolysaccharide (LPS) (a product of bacterial infection), the pro-inflammatory cytokine TNF is released. Cpn10 has been shown to suppress production of TNF on challenge of cells with LPS, while increasing the levels of the anti-inflammatory cytokine IL-10. Investigating the role of Cpn10 in modulating inflammation will contribute to the understanding and treatment of diseases associated with inflammation, including multiple sclerosis and rheumatoid arthritis.Read moreRead less