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
Elucidating the post-transcriptional regulation of mast cell proteases. Mast cells (MCs) are immune cells that protect against pathogens but may induce deleterious inflammation. MC function is mediated by specific proteases that are pre-formed and stored in granules. These proteases have unique yet poorly understood mechanisms of regulation. The aim of the project is to use a novel suite of molecular tools and genetically modified mice to identify the critical regions of transcripts that post-tr ....Elucidating the post-transcriptional regulation of mast cell proteases. Mast cells (MCs) are immune cells that protect against pathogens but may induce deleterious inflammation. MC function is mediated by specific proteases that are pre-formed and stored in granules. These proteases have unique yet poorly understood mechanisms of regulation. The aim of the project is to use a novel suite of molecular tools and genetically modified mice to identify the critical regions of transcripts that post-transcriptionally regulate the production and storage of these proteins. The project aims to identify the RNA binding proteins, microRNAs and other novel factors that also regulate them. This is expected to elucidate the post-transcriptional mechanisms of regulation of MC proteases.Read moreRead less
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
Cellular mechanisms that protect against copper-bound beta-amyloid. This project will investigate some of the brain’s own mechanisms for protecting itself against Alzheimer’s disease. Understanding these mechanisms will be important for developing future therapeutic strategies for treating Alzheimer’s disease.
Real-time imaging of the initiation of adaptive immunity in vivo. Understanding the first few hours of an immune response is fundamental to understanding how the human immune system functions. The immune system mounts our responses to infectious diseases, but can also cause autoimmune disease, allergy, and organ graft rejection. We will study how naive antigen-specific T cells first contact antigen in lymph nodes using 2-photon intravital microscopy. The research has the potential to change the ....Real-time imaging of the initiation of adaptive immunity in vivo. Understanding the first few hours of an immune response is fundamental to understanding how the human immune system functions. The immune system mounts our responses to infectious diseases, but can also cause autoimmune disease, allergy, and organ graft rejection. We will study how naive antigen-specific T cells first contact antigen in lymph nodes using 2-photon intravital microscopy. The research has the potential to change the way we think about the clonal selection of lymphocytes, the fundamental theory underlying our understanding of the immune system.Read moreRead less
CD4 T cell programming by neonatal and early-life infection. T lymphocytes (T cells) are white blood cells that play a critical role in protecting the body from infection. Before T cells can function they need to be programmed so that they can specifically respond to an infectious agent (a type of bacteria or virus). Inappropriate programming can lead to disease. Whether T cells respond to an infectious agent or foreign substance in a protective or destructive manner may critically depend on the ....CD4 T cell programming by neonatal and early-life infection. T lymphocytes (T cells) are white blood cells that play a critical role in protecting the body from infection. Before T cells can function they need to be programmed so that they can specifically respond to an infectious agent (a type of bacteria or virus). Inappropriate programming can lead to disease. Whether T cells respond to an infectious agent or foreign substance in a protective or destructive manner may critically depend on the age that an individual first encounters the infection. Our project will identify critical periods in life that direct T cell programming to subsequent protective or destructive responses, providing new insights into the developing immune system that may be exploited to treat disease or develop vaccines.Read moreRead less
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
Development of microbial bioproducts for the suppression of inflammation. Asthma and inflammatory diseases are serious health problems that result from excessive inflammation. Exposure to bacteria may reduce inflammation. This project will identify the bacterial components that reduce inflammation and develop them into new anti-inflammatory therapies for asthma.
Understanding the dynamics of T cell responses to chronic infection. The health, social, and economic impact of chronic infections on the Australian and global populations is enormous. A major obstacle to the development of vaccines against chronic infections is that we have a poor understanding of immune responses to persistent infections. We aim to use bioinformatics and mathematical modelling to understand immune responses to persistent viruses so that we can improve the long-term immune cont ....Understanding the dynamics of T cell responses to chronic infection. The health, social, and economic impact of chronic infections on the Australian and global populations is enormous. A major obstacle to the development of vaccines against chronic infections is that we have a poor understanding of immune responses to persistent infections. We aim to use bioinformatics and mathematical modelling to understand immune responses to persistent viruses so that we can improve the long-term immune control of chronic viral infections such as the human immunodeficiency virus (HIV). This project will strengthen Australian research in the area of interdisciplinary approaches to immunology, which is becoming crucial to interpreting the rapidly increasing volume of data obtained using advanced experimental techniques.Read moreRead less