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
The regulation of signalling molecules in Saccharomyces Cerevisiae by inositol polyphosphate 5-phosphatases. Phosphoinositide signalling molecules regulate the actin cytoskeleton, secretion, vesicular trafficking and cell growth and death. We have identified, cloned and characterised a family of signal terminating enzymes called inositol polyphosphate 5-phosphatases (5-phosphatases) that regulate phosphoinositide signalling molecules. We have cloned and characterised four distinct 5-phosphatases ....The regulation of signalling molecules in Saccharomyces Cerevisiae by inositol polyphosphate 5-phosphatases. Phosphoinositide signalling molecules regulate the actin cytoskeleton, secretion, vesicular trafficking and cell growth and death. We have identified, cloned and characterised a family of signal terminating enzymes called inositol polyphosphate 5-phosphatases (5-phosphatases) that regulate phosphoinositide signalling molecules. We have cloned and characterised four distinct 5-phosphatases in the yeast Saccharomyces Cerevisiae and demonstrated by both deletion and overexpression studies that these enzymes regulate the actin cytoskeleton, endocytosis and secretion. This research proposal aims to investigate the signalling complexes the 5-phosphatases form with specific actin binding and or regulatory proteins, investigate the complex interactions of phosphoinositide lipid phosphatases and the roles they play in regulating secretion from the endoplasmic reticulum and finally characterize a novel 5-phosphatase that we have recently identified. Collectively the outcome of these studies will provide novel information about the functionallly significant signalling pathways regulated by this important enzyme family.Read moreRead less
Nuclear plasticity during neutrophil migration and function. This project aims to discover how nuclear shape affects neutrophil function. Cell migration needs overall cellular plasticity and plasticity of internal structures such as the nucleus. The neutrophil, one of the most peripatetic cell types, has a specialised lobulated nucleus, thought to facilitate its mobility and function. Using zebrafish reporter lines that concurrently display the nucleus and cytoplasm, this project will display th ....Nuclear plasticity during neutrophil migration and function. This project aims to discover how nuclear shape affects neutrophil function. Cell migration needs overall cellular plasticity and plasticity of internal structures such as the nucleus. The neutrophil, one of the most peripatetic cell types, has a specialised lobulated nucleus, thought to facilitate its mobility and function. Using zebrafish reporter lines that concurrently display the nucleus and cytoplasm, this project will display the dynamic plasticity of neutrophil nuclei during neutrophil migration and function in vivo. This project seeks to use the spatiotemporal resolution of a lattice light sheet microscope to examine this further, and explore its effect on neutrophil function. The project seeks to establish morphological and mechanical principles applying not just to neutrophils, but to all migratory cell types.Read moreRead less
Functional Genomic Analysis of Exported DNAJ Molecules in the Malaria Parasite Plasmodium falciparum. Malaria is not only a global health problem, but also affects countries surrounding Australia like PNG and Indonesia, reducing the region's stability and prosperity. Environmental changes and increased mobility of people (eg. aid and security personnel) make Australia itself more prone to malaria. The project will translate recent genomic data into functional insights using frontier technology t ....Functional Genomic Analysis of Exported DNAJ Molecules in the Malaria Parasite Plasmodium falciparum. Malaria is not only a global health problem, but also affects countries surrounding Australia like PNG and Indonesia, reducing the region's stability and prosperity. Environmental changes and increased mobility of people (eg. aid and security personnel) make Australia itself more prone to malaria. The project will translate recent genomic data into functional insights using frontier technology to identify new intervention targets for P. falciparum infection. Developing novel targets is mandated by humanity, and also to safeguard Australia's region against the social and economical implication of this disease. An Australian developed intervention would increase the global visibility of its science, leading to increased investments.Read moreRead less
The role of PtdIns(4,5)P2 in cellular responses in Saccharomyces cerevisiae. This grant application falls under the criteria of frontier technologies in genomics/phenomics and complex systems. We are characterizing a highly conserved network of signaling molecules regulated by complex large families of enzymes that regulate the bending of membranes, and cellular events including cell division in plants, yeast and mammalian cells. We have developed cutting edge novel technologies to localize sign ....The role of PtdIns(4,5)P2 in cellular responses in Saccharomyces cerevisiae. This grant application falls under the criteria of frontier technologies in genomics/phenomics and complex systems. We are characterizing a highly conserved network of signaling molecules regulated by complex large families of enzymes that regulate the bending of membranes, and cellular events including cell division in plants, yeast and mammalian cells. We have developed cutting edge novel technologies to localize signaling on specific intracellular membranes and visualise the role cellular lipids play in forming tubules in cells. This project will result in the presentation of Australian research at international forums and support the training of PhD students.Read moreRead less
Regulation of local lymphocyte trafficking and its role during infection. The study of early immune responses will contribute to the development of better vaccination strategies. In particular it will contribute by helping to understand the essential differences between reactogenicity and immunogenicity and how this relates to adjuvants. Using this understanding it will be possible to develop novel adjuvants that induce appropriate immunity with minimal side effects.
How cell shape regulators control cell competition in tissue development. This project aims to determine how cell shape (polarity) regulators affect cell survival in an epithelial tissue. When mutation or wounding perturb cell shape regulators in a tissue cell, signalling pathways are altered that kill the aberrant cells. A surveillance mechanism termed "cell competition" is important to remove the damaged cells. This project will investigate a potential regulator of cell competition, the tyrosi ....How cell shape regulators control cell competition in tissue development. This project aims to determine how cell shape (polarity) regulators affect cell survival in an epithelial tissue. When mutation or wounding perturb cell shape regulators in a tissue cell, signalling pathways are altered that kill the aberrant cells. A surveillance mechanism termed "cell competition" is important to remove the damaged cells. This project will investigate a potential regulator of cell competition, the tyrosine phosphatase PTP61F, in response to perturbation of cell shape regulators, using the vinegar fly, Drosophila, and mammalian systems. This study is expected to reveal biomarkers that can be used to improve organismal fitness to increase productivity or to decrease it for pest control.Read moreRead less
Development of Model Systems to Investigate Blood Hydrodynamic Parameters Affecting Blood Cell Function: An Interdisciplinary Approach. National benefit will come through this research contributing to a better understanding of blood flow biology and pathology, both of which are of particular relevance to the aging Australian population. This benefit is well aligned with the 2008 National research priority 2: Promoting and Maintaining Good Health; Priority Goal 3. Preventative Health. The synthes ....Development of Model Systems to Investigate Blood Hydrodynamic Parameters Affecting Blood Cell Function: An Interdisciplinary Approach. National benefit will come through this research contributing to a better understanding of blood flow biology and pathology, both of which are of particular relevance to the aging Australian population. This benefit is well aligned with the 2008 National research priority 2: Promoting and Maintaining Good Health; Priority Goal 3. Preventative Health. The synthesis of both extensive expertise in platelet/cardiovascular research and bioengineering/rheology should provide a substantial platform from which fundamental new discoveries in this niche area can be made. The development of novel platelet analysis tools arising from this work may also ultimately lead to new intellectual property and attract industry based funding.Read moreRead less
Proteomic and Transcriptional Profiling of Cartilage. Gene expression and signalling pathways that regulate cartilage formation, and its orderly transition to bone, are poorly described. Our studies will, for the first time, combine two complementary cutting-edge approaches, protein identification by proteomic analysis, and mRNA profiling by microarray analysis, to define these pathways and develop a comprehensive catalogue of proteins and gene expression patterns during cartilage development a ....Proteomic and Transcriptional Profiling of Cartilage. Gene expression and signalling pathways that regulate cartilage formation, and its orderly transition to bone, are poorly described. Our studies will, for the first time, combine two complementary cutting-edge approaches, protein identification by proteomic analysis, and mRNA profiling by microarray analysis, to define these pathways and develop a comprehensive catalogue of proteins and gene expression patterns during cartilage development and bone formation. This information will provide insight into the regulation of cartilage differentiation, maturation and structure, and will provide a critical platform for the development of more sophisticated cartilage and bone biomaterials for improved tissue repair and regeneration.Read moreRead less