Investigating the evolution of innate and adaptive cellular immunity. This proposal aims to assess the impact of geographical and genetic isolation of the Australian Indigenous population on adaptive and innate immune systems. The project will use novel DNA sequencing approaches to generate the high resolution sequences of two genetic loci that regulate innate and adaptive immune responses, the major histocompatibility complex locus and the killer cell immunoglobulin-like receptor locus. In an i ....Investigating the evolution of innate and adaptive cellular immunity. This proposal aims to assess the impact of geographical and genetic isolation of the Australian Indigenous population on adaptive and innate immune systems. The project will use novel DNA sequencing approaches to generate the high resolution sequences of two genetic loci that regulate innate and adaptive immune responses, the major histocompatibility complex locus and the killer cell immunoglobulin-like receptor locus. In an initial screen, distinct variants and combinations of these genes were identified. This project aims to interrogate how variation in these critical genes impacts on the function of cytotoxic lymphocytes, providing insights into the evolutionary drivers of immune recognition mechanisms.Read moreRead less
Gas Phase Reactivity of Charged Peptide and DNA Radicals: Fundamentals and Applications. Radicals derived from the "molecules of life", proteins and DNA, play both beneficial (e.g. enzyme catalysis) and deleterious roles (e.g. protein and DNA damage associated with disease). Two electrospray ionisation mass spectrometry approaches have been discovered to generate charged radicals of related models systems (e.g. peptides and nucleobases). The gas phase chemistry of these species is a largely unch ....Gas Phase Reactivity of Charged Peptide and DNA Radicals: Fundamentals and Applications. Radicals derived from the "molecules of life", proteins and DNA, play both beneficial (e.g. enzyme catalysis) and deleterious roles (e.g. protein and DNA damage associated with disease). Two electrospray ionisation mass spectrometry approaches have been discovered to generate charged radicals of related models systems (e.g. peptides and nucleobases). The gas phase chemistry of these species is a largely unchartered area! We will examine the fundamental chemistry (unimolecular and bimolecular reactions) of these systems and build upon some exciting preliminary results which suggest potential applications (e.g. as a proteomics tool to sequence and distinguish between leucine and isoleucine residues in peptides).Read moreRead less
Structure and activity of host-defence peptides from Australian anurans: anticancer agents, neuropeptides and nNOS inhibitors. We have discovered peptides that may have clinical applications. This is significant as these molecules may have one or more of the following properties. They may have anti-cancer effects; they may increase the effectiveness of the immune system by enhancing lymphocyte formation; and, they may act to reduce inflammation, stroke or cardiac conditions by controlling nitri ....Structure and activity of host-defence peptides from Australian anurans: anticancer agents, neuropeptides and nNOS inhibitors. We have discovered peptides that may have clinical applications. This is significant as these molecules may have one or more of the following properties. They may have anti-cancer effects; they may increase the effectiveness of the immune system by enhancing lymphocyte formation; and, they may act to reduce inflammation, stroke or cardiac conditions by controlling nitric oxide formation. Another national benefit is that personnel involved in this project are trained to the highest international standards in peptide chemistry/mass spectrometry/nuclear magnetic resonance: currently, there are not enough trained scientists in this area to meet demand.Read moreRead less
Biologically active peptides and proteins from anurans: the relationship between structure and activity. We have identified peptides (from glands of frogs and toads), some of which are amongst the most powerful biologically active compounds in the animal kingdom. The aims of this project are to investigate the relationship between the structure and bioactivity of chosen groups of peptides including pheromones, anticancer and antibiotic peptides, and peptides which inhibit neuronal nitric oxide ....Biologically active peptides and proteins from anurans: the relationship between structure and activity. We have identified peptides (from glands of frogs and toads), some of which are amongst the most powerful biologically active compounds in the animal kingdom. The aims of this project are to investigate the relationship between the structure and bioactivity of chosen groups of peptides including pheromones, anticancer and antibiotic peptides, and peptides which inhibit neuronal nitric oxide synthase. It would be of national benefit if any of these peptides have applied application, e.g. if we can use the sex pheromone of the cane toad to reduce its population, or if we can produce an anticancer active peptide of clinical applicability.Read moreRead less
Pushing the Boundaries of Multi-modal Biospectroscopic Microscopies. In order to understand the fundamentals of life processes, diseases, and their treatments, it is essential to probe fundamental changes in molecular processes in cells, tissues and whole organisms. Much of our understanding of these processes has involved the introduction of chemical probes for biospectroscopy, but these have inherent problems because the probe can often change the biochemistry that is being probed. This projec ....Pushing the Boundaries of Multi-modal Biospectroscopic Microscopies. In order to understand the fundamentals of life processes, diseases, and their treatments, it is essential to probe fundamental changes in molecular processes in cells, tissues and whole organisms. Much of our understanding of these processes has involved the introduction of chemical probes for biospectroscopy, but these have inherent problems because the probe can often change the biochemistry that is being probed. This project will push the boundaries of a variety of micro and nano "probe-free" microscopies to provide fundamental insights into these life processes, which could ultimately lead to improvements in the diagnosis, prevention and treatment of diseases.Read moreRead less
Molecular insights into bacterial metal ion homeostasis and toxicity. This project aims to measure bacterial cellular metal concentrations, elucidate mechanisms cells use to adapt to changing extracellular metal concentrations, and reveal the molecular targets of metal toxicity. Metal ions are essential to all forms of life, and half of all proteins use metal ions for cellular chemical processes. However, how cells precisely balance sufficient metal ions for essential cellular chemistry without ....Molecular insights into bacterial metal ion homeostasis and toxicity. This project aims to measure bacterial cellular metal concentrations, elucidate mechanisms cells use to adapt to changing extracellular metal concentrations, and reveal the molecular targets of metal toxicity. Metal ions are essential to all forms of life, and half of all proteins use metal ions for cellular chemical processes. However, how cells precisely balance sufficient metal ions for essential cellular chemistry without accumulating a toxic excess (metal homeostasis) is poorly understood. Discovering the roles of metal ions in bacterial cells will be key to defining the chemical biology of living systems and will provide information essential to understanding how microbes adapt to changing environments.Read moreRead less
Skeletal endocrine signalling in the regulation of glucose metabolism. This project seeks to explore a highly novel and interesting recent development in bone biology: the fact that the skeleton is a central regulator of glucose metabolism. Currently, the mechanisms involved in this process remain unclear. mTORC1 has been identified as a signalling pathway in bone cells that modulates glucose metabolism. This project plans to selectively delete mTORC1 in the bone cells of mice to examine how ske ....Skeletal endocrine signalling in the regulation of glucose metabolism. This project seeks to explore a highly novel and interesting recent development in bone biology: the fact that the skeleton is a central regulator of glucose metabolism. Currently, the mechanisms involved in this process remain unclear. mTORC1 has been identified as a signalling pathway in bone cells that modulates glucose metabolism. This project plans to selectively delete mTORC1 in the bone cells of mice to examine how skeletal mTORC1 signalling regulates glucose metabolism, and identify novel pathways and circulating factors involved in this process. These studies may provide greater understanding of the basic biology of glucose metabolism, and may have applications in animal husbandry and the future management of diabetes.Read moreRead less
Evolution and function of mammalian sex chromosomes. Research on iconic Australian mammals has profoundly reshaped our understanding of reproductive biology and sex chromosome evolution. In this project we combine unique expertise, international collaboration and novel genetic information about Australia's unique egg-laying mammals (echidna and platypus) to investigate major aspects of reproduction. This work will address fundamental aspects of sex chromosome biology and advance our understandin ....Evolution and function of mammalian sex chromosomes. Research on iconic Australian mammals has profoundly reshaped our understanding of reproductive biology and sex chromosome evolution. In this project we combine unique expertise, international collaboration and novel genetic information about Australia's unique egg-laying mammals (echidna and platypus) to investigate major aspects of reproduction. This work will address fundamental aspects of sex chromosome biology and advance our understanding of mammalian reproduction. The knowledge gained will have application in captive breeding and conservation of these extraordinary Australian mammals. The project also provides opportunity to train research students in cutting edge molecular biology and informatics.Read moreRead less
The genetic regulation of organogenesis: endoderm development in the Drosophila embryo. Embryonic development is an important research field in biology, not only for its extraordinary complexity but also because of the insights it provides into molecular processes that underpin a variety of diseases. This project aims to discover genes and molecules that regulate the normal development of one of the most important organs, the gut.