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
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
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.
Angiogenic defects in mutant growth plate cartilage reveal new modulators of vascular invasion. Converting cartilage to bone requires blood vessel invasion from the bony interface. This project will test, in vitro and in vivo, the hypothesis that collagen fragments regulate blood vessel invasion into cartilage. This data will have implications for processes requiring new blood vessels such as bone growth, cancer, inflammation and ischemia.
Characterisation of plant cysteine proteases with therapeutic potential. This project aims to uncover how plant enzymes have effects on the immune system. This will allow the development of these enzymes as therapeutic agents for cancer and autoimmune conditions.
Structural basis of the neuroendocrine enzyme GAD65-mediated autoimmunity in Type 1 Diabetes. More than 80 per cent of patients with Type 1 Diabetes develop antibodies against the neuroendocrine enzyme GAD65. This project will use state-of-the art techniques to study the interaction of GAD65 with antibodies in molecular detail. This will provide key insights into the molecular mechanisms of autoimmune disease.
The discovery and characterisation of novel protein regulators of blood cell formation. All of the mature blood cells in the human body are derived from a common ancestor cell type known as a stem cell. Our proposed studies will enhance our knowledge of how functional, mature blood cells are formed from stem cells and how dysregulation of these normally tightly controlled pathways can give rise to severe blood diseases.