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
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
Surface Chemistry meets Cell Biology: Molecular Level Control of Surface Architecture for Cell Adhesion and Migration. Biotechnological applications such as tissue engineering, bone supports, implantable materials, cell assays and biosensors all require detailed knowledge of how cells interact with their environment. The proposed research aims to provide this knowledge by developing unique modified surfaces to investigate white blood cell migration and adhesion. Additional expected outcome will ....Surface Chemistry meets Cell Biology: Molecular Level Control of Surface Architecture for Cell Adhesion and Migration. Biotechnological applications such as tissue engineering, bone supports, implantable materials, cell assays and biosensors all require detailed knowledge of how cells interact with their environment. The proposed research aims to provide this knowledge by developing unique modified surfaces to investigate white blood cell migration and adhesion. Additional expected outcome will contribute to our understanding of the many fundamental cellular processes such as cell growth, differentiation and cell death as well as the molecular basis of diseases such as inflammation, cancer, cardiovascular diseases and wound healing. This research program will establish Australia as a leading force in this new research field.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100150
Funder
Australian Research Council
Funding Amount
$500,000.00
Summary
Beyond Proteomics: structure and function of protein modifications. The world's leading cancer therapeutics have come from the protein phosphorylation field, and glycomics has led to drugs that combat the flu and that stimulate red blood cell production in cancer patients. Thus there is a bright future for discovery of new medicines based on new knowledge in this area. Protein modifications are key to the understanding of disease mechanisms and for searching for new disease markers and new the ....Beyond Proteomics: structure and function of protein modifications. The world's leading cancer therapeutics have come from the protein phosphorylation field, and glycomics has led to drugs that combat the flu and that stimulate red blood cell production in cancer patients. Thus there is a bright future for discovery of new medicines based on new knowledge in this area. Protein modifications are key to the understanding of disease mechanisms and for searching for new disease markers and new therapeutics. In the hands of local experts the instruments will enable identification of these modifications and provide improved understanding of biology, increase the national competitiveness of Australia's scientists, and provide advanced technology training to the next generation of scientists.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
CD151 and functional overlap in tetraspanins. The applicants are currently world leaders in the tetraspanin field. This project will enhance existing international collaborations to maintain and increase the applicants', and hence Australia's, international standing in this field and Australia's reputation in cell and molecular biology in general.
The project will greatly increase our understanding of this important but poorly understood family of proteins. It will also provide training opport ....CD151 and functional overlap in tetraspanins. The applicants are currently world leaders in the tetraspanin field. This project will enhance existing international collaborations to maintain and increase the applicants', and hence Australia's, international standing in this field and Australia's reputation in cell and molecular biology in general.
The project will greatly increase our understanding of this important but poorly understood family of proteins. It will also provide training opportunities for postgraduate students in state-of-the-art approaches in biotechnology.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
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
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