An X-ray crystallographic investigation into co-receptors on T-lymphocytes. T lymphocytes are an indispensable cellular component of the immune system. The normal process of T cell selection in the thymus, and the ability of mature T cells to respond to foreign antigens are governed by receptor recognition and co-receptor mediated events. The co-receptors encompass a wide spectrum of structurally diverse proteins that are involved in adhesion, co-ligation and signal transduction. This proposa ....An X-ray crystallographic investigation into co-receptors on T-lymphocytes. T lymphocytes are an indispensable cellular component of the immune system. The normal process of T cell selection in the thymus, and the ability of mature T cells to respond to foreign antigens are governed by receptor recognition and co-receptor mediated events. The co-receptors encompass a wide spectrum of structurally diverse proteins that are involved in adhesion, co-ligation and signal transduction. This proposal aims to investigate, using X-ray crystallography as the primary research tool, co- receptors located on T-lymphocytes. This work will gain fundamental insights into co-receptor function.Read moreRead less
A Structural Investigation Into Events Within The Immunological Synapse. The proposed research program, using laboratory-based and synchrotron-based radiation, will provide significant fundamental insight into the processes that control infection. Investigating processes central to immunity is important, as it will further our understanding of these critically-important events. Such knowledge will increase Australia's international research standing, as well as having the potential to generat ....A Structural Investigation Into Events Within The Immunological Synapse. The proposed research program, using laboratory-based and synchrotron-based radiation, will provide significant fundamental insight into the processes that control infection. Investigating processes central to immunity is important, as it will further our understanding of these critically-important events. Such knowledge will increase Australia's international research standing, as well as having the potential to generate novel therapies, such as immunosuppressants.Read moreRead less
A New Model for 3D Migration Involving Claw Structures and Metalloproteinases. This proposal will revolutionize ideas related to cell movement through three-dimensional (3D) matrix. Our method in mimicking the body's dense 3D matrix environment have led to the discovery of a new cell structure called Claws, and the formulation of a new model for 3D invasion in high density matrix. We will study the genes that control this type of migration including those involved in the formation of the cell fr ....A New Model for 3D Migration Involving Claw Structures and Metalloproteinases. This proposal will revolutionize ideas related to cell movement through three-dimensional (3D) matrix. Our method in mimicking the body's dense 3D matrix environment have led to the discovery of a new cell structure called Claws, and the formulation of a new model for 3D invasion in high density matrix. We will study the genes that control this type of migration including those involved in the formation of the cell front (Claw region), the back of the cells and matrix digestion. This work will have significant impact on normal and pathological human conditions from immune responses to tissue regeneration and cancer.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
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
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
Body fluids: sweet protection against infection? Serious health problems caused by pathogenic microorganisms are in sharp increase due to aging population, escalating numbers of immunocompromised people and the increased resistance of microorganisms to currently available antibiotics. Our research will lead to development of new approaches to protect people and animals from pathogens before they invade the body. The commercial possibilities for new and natural antimicrobials are present from bot ....Body fluids: sweet protection against infection? Serious health problems caused by pathogenic microorganisms are in sharp increase due to aging population, escalating numbers of immunocompromised people and the increased resistance of microorganisms to currently available antibiotics. Our research will lead to development of new approaches to protect people and animals from pathogens before they invade the body. The commercial possibilities for new and natural antimicrobials are present from both the health and agricultural sectors in Australia and abroad. The technologies used and further developed will serve as a state-of-the-art training ground for the next generation of postgraduate students encompassing the integration of genomics, proteomics and glycomics technologies.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
GENOMIC/PHENOMIC IDENTIFICATION AND CHARACTERISATION OF NOVEL HEMATOPOIETIC REGULATORS. Blood cells are fundamental to health. They play a vital role in maintaining the condition of tissues and organs, fight infections and are essential players in the body's response to injury. Understanding how blood cells are produced and how they function is critical to improving the treatment of disease. With the sequencing of the genome, we now have the tools we need to find the genes controlling these proc ....GENOMIC/PHENOMIC IDENTIFICATION AND CHARACTERISATION OF NOVEL HEMATOPOIETIC REGULATORS. Blood cells are fundamental to health. They play a vital role in maintaining the condition of tissues and organs, fight infections and are essential players in the body's response to injury. Understanding how blood cells are produced and how they function is critical to improving the treatment of disease. With the sequencing of the genome, we now have the tools we need to find the genes controlling these processes. This project will harness the power of modern genetic technologies to dissect the role of novel genes involved in blood cell formation and function, and will open up new therapeutic opportunities for treating the many diseases associated with dysregulation of this important cell system. Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0668413
Funder
Australian Research Council
Funding Amount
$723,000.00
Summary
The Nanoscale Characterisation Centre WA Analytical Biological Transmission Electron Microscope Facility. A new regional analytical biological TEM (BioTEM) will provide critical support to acclaimed medical and biological groups researching nationally significant age-related health, agricultural and environmental questions. The BioTEM, for example, will allow a unique opportunity to detect metal uptake and accumulation in bone-forming cells. This research will provide insight into metal induce ....The Nanoscale Characterisation Centre WA Analytical Biological Transmission Electron Microscope Facility. A new regional analytical biological TEM (BioTEM) will provide critical support to acclaimed medical and biological groups researching nationally significant age-related health, agricultural and environmental questions. The BioTEM, for example, will allow a unique opportunity to detect metal uptake and accumulation in bone-forming cells. This research will provide insight into metal induced afflictions, such as nasal ulcer, lung cancer, contact dermatitis and hypersensitivity reactions like asthma. The BioTEM will also be used to study how plants take up nutrients and how they use these compounds for growth, development and reproduction. Successes in this research will transfer to the important development of salt-tolerant plant species.Read moreRead less