The Immunoregulatory Role of the Endogenous Cannabinoid Anandamide. Anandamides are naturally occurring fatty acids that act at the cannabinoid receptor expressed in the brain and periphery. A new proposal by our research group challenges traditional models of the disease process by suggesting that the anandamide system is an important imunoregulatory system that can be targeted by invading pathogens. We propose that disruption to the anandamide system, by bacteria or viruses acting at the rece ....The Immunoregulatory Role of the Endogenous Cannabinoid Anandamide. Anandamides are naturally occurring fatty acids that act at the cannabinoid receptor expressed in the brain and periphery. A new proposal by our research group challenges traditional models of the disease process by suggesting that the anandamide system is an important imunoregulatory system that can be targeted by invading pathogens. We propose that disruption to the anandamide system, by bacteria or viruses acting at the receptor to block immunological responses, contributes to chronic illness states. At this point we have good evidence that anandamides are immunoregulators, however, we have very little knowledge of their precise physiological role. The aim of this research is to begin to characterise the immunoregulatory role of the anandamide system. This project will provide a comprehensive understanding of this endogenous control system, the immunological properties of which have not previously been described. The outcome of this research may lead to the identification of new avenues for the development of pharmaceutical interventions that can target this system.Read moreRead less
THE MATERNAL GUT MICROBIOTA DRIVES FOETAL THYMIC T CELL DEVELOPMENT . This project aims to investigate the role of maternal gut microbiota on foetal immune development, revealing the interaction of gut microbiota-host immunity at the early stages of new life. Significantly, the research will examine the time window when microbiota by-products from the mother reach the foetus and affect the development of immunity. Maternal by-products will be identified using cutting-edge methods to unravel the ....THE MATERNAL GUT MICROBIOTA DRIVES FOETAL THYMIC T CELL DEVELOPMENT . This project aims to investigate the role of maternal gut microbiota on foetal immune development, revealing the interaction of gut microbiota-host immunity at the early stages of new life. Significantly, the research will examine the time window when microbiota by-products from the mother reach the foetus and affect the development of immunity. Maternal by-products will be identified using cutting-edge methods to unravel the complex systems interactions in the developmental process. Outcomes include new fundamental knowledge about maternal gut microbiota composition and its relationship to the growing foetus, with benefits in informing pregnant women about their lifestyle choices, particularly their dietary habits, during pregnancy.
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The macrophage nucleus - its form and function during migration in vivo. As cells migrate through tissues, they encounter complex, 3-dimensional environments that provide cues to guide them and present obstacles in their path. This project focuses on macrophages, a large immune cell capable of both amoeboid and mesenchymal modes of migration. The nucleus is the largest organelle and its bulk and stiffness must be managed as migrating cells travel through constrictions. The project uses specialis ....The macrophage nucleus - its form and function during migration in vivo. As cells migrate through tissues, they encounter complex, 3-dimensional environments that provide cues to guide them and present obstacles in their path. This project focuses on macrophages, a large immune cell capable of both amoeboid and mesenchymal modes of migration. The nucleus is the largest organelle and its bulk and stiffness must be managed as migrating cells travel through constrictions. The project uses specialised high-end microscopy and genetic methods to examine how the nucleus of migrating zebrafish macrophages deforms, repositions and is restructured during migration in living tissues, and how this influences macrophage locomotion. The goal is to provide fundamental insights into the cell biology of macrophage migration.Read moreRead less
Transduction of neuronal signals by brain macroglial cells: implications for neuronal function. Study of mechanisms regulating brain cell (neuron and glial) communication is essential for understanding of normal brain function and transformations that occur in neurodegenerative states and age-related disorders. Mechanisms underlying neuron-glia communication are not well understood. By combining cell physiology, digital imaging technologies, and genetically designed and delivered molecules we w ....Transduction of neuronal signals by brain macroglial cells: implications for neuronal function. Study of mechanisms regulating brain cell (neuron and glial) communication is essential for understanding of normal brain function and transformations that occur in neurodegenerative states and age-related disorders. Mechanisms underlying neuron-glia communication are not well understood. By combining cell physiology, digital imaging technologies, and genetically designed and delivered molecules we will enhance our understanding of this brain cell communication and critical roles played by intracellular calcium. This will enhance international competitiveness of Australian biological research and provide novel insight of glial function in neurodegeneration and potential for specific therapeutic intervention in disease.Read moreRead less
Huntingtin-associated protein 1 controls cell communication. The purpose of this study is to identify the mechanisms by which a novel regulator of cell communication which we have identified is able to control the release of chemical signals from a cell. This project will provide critical insight into a cellular pathway that underlies hormone secretion, neurotransmission and higher brain functions.
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.
Mechanism of transmission of calcium waves by glial cells. This research concerns determining the fundamental properties of cells that occupy about 70% of the brain, the glial cells. Two very important discoveries on glial cells have recently been made, namely that they can convey information in the form of patterns of waves and that they possess molecules on their surface membranes that have been implicated in psychotic disorders. One such molecule is called the D2 receptor and its malfunctioni ....Mechanism of transmission of calcium waves by glial cells. This research concerns determining the fundamental properties of cells that occupy about 70% of the brain, the glial cells. Two very important discoveries on glial cells have recently been made, namely that they can convey information in the form of patterns of waves and that they possess molecules on their surface membranes that have been implicated in psychotic disorders. One such molecule is called the D2 receptor and its malfunctioning has been implicated in schizophrenia. Our research will determine the way in which information is propagated in the glial system of the brain and also illuminate the function of several of the molecules found on the surface of the glial cells.Read moreRead less
Neuron-microglia signalling mechanisms. This research concerns determining the fundamental mechanisms by which one of the principal non-neuronal cells in the brain , the microglial cell, interacts with neurons to change their properties. The correct functioning of neural networks is necessary for our normal behaviour. Such networks can be disrupted and indeed destroyed by the release of inflammatory molecules from microglial cells. In this work the way in which anti-inflammatory molecules are re ....Neuron-microglia signalling mechanisms. This research concerns determining the fundamental mechanisms by which one of the principal non-neuronal cells in the brain , the microglial cell, interacts with neurons to change their properties. The correct functioning of neural networks is necessary for our normal behaviour. Such networks can be disrupted and indeed destroyed by the release of inflammatory molecules from microglial cells. In this work the way in which anti-inflammatory molecules are released from the microglia will be elucidated, thus providing insight into how to prevent the destructive actions of the inflammatory molecules on the nervous system. Read moreRead less
Assessing the physiological roles of ubiquitination in regulating neuronal ion channels, receptors and transporters. Significant alterations in the activity neuronal transporters and receptors occur during tissue injury and regeneration as well as in many neurodegenerative disease states. Modulation of the pathways that control these transporters is an emerging therapeutic target, however, the molecular basis of these control mechanisms remain poorly understood. The outcome of this project will ....Assessing the physiological roles of ubiquitination in regulating neuronal ion channels, receptors and transporters. Significant alterations in the activity neuronal transporters and receptors occur during tissue injury and regeneration as well as in many neurodegenerative disease states. Modulation of the pathways that control these transporters is an emerging therapeutic target, however, the molecular basis of these control mechanisms remain poorly understood. The outcome of this project will be a thorough characterisation of a novel regulatory paradigm in neurons that is likely to be crucial for neuronal development and regeneration, and will potentially provide novel therapeutic targets for various neuronal diseases.Read moreRead less
G-protein coupled receptor-mediated calcium signalling in parasympathetic neurons. External chemical stimuli act on specific cell-surface receptors of neurons resulting in an increase in the intracellular calcium ion concentration which acts as a second messenger to alter neuronal excitability. There are, however, many receptors acting through a number of closely related proteins involving complex intracellular signalling pathways which remain poorly understood. This project uses molecular, elec ....G-protein coupled receptor-mediated calcium signalling in parasympathetic neurons. External chemical stimuli act on specific cell-surface receptors of neurons resulting in an increase in the intracellular calcium ion concentration which acts as a second messenger to alter neuronal excitability. There are, however, many receptors acting through a number of closely related proteins involving complex intracellular signalling pathways which remain poorly understood. This project uses molecular, electrical and fluorescence techniques to elucidate the molecular basis for these interactions by identifying the roles individual proteins play in integrating diverse extracellular stimuli and neuronal excitablility in the peripheral nervous system.Read moreRead less