Novel mechanisms of bacterial arsenic metabolism - arsenate reduction and arsenite oxidation. Novel arsenic metabolising bacteria (i.e., arsenate respiring and arsenite oxidising), which are both phylogenetically and physiologically unique, have been isolated from arsenic-contaminated areas in Australia. The arsenate respiring bacterium, Chrysiogenes arsenatis, is of particular interest as it is the only organism reported able to respire with arsenate using the respiratory substrate acetate as t ....Novel mechanisms of bacterial arsenic metabolism - arsenate reduction and arsenite oxidation. Novel arsenic metabolising bacteria (i.e., arsenate respiring and arsenite oxidising), which are both phylogenetically and physiologically unique, have been isolated from arsenic-contaminated areas in Australia. The arsenate respiring bacterium, Chrysiogenes arsenatis, is of particular interest as it is the only organism reported able to respire with arsenate using the respiratory substrate acetate as the electron donor. It is proposed that physiological, biochemical and molecular biological studies be carried out to better understand the mechanisms by which these organisms metabolise arsenic. The knowledge gained from these studies will have worldwide application in the development of an arsenic bioremediation system.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
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
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.
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.