CX3C chemokine signalling in the olfactory epithelium and its role in the self regeneration of the olfactory system. The current proposal will explore new venues in adult neural stem cell research and contribute to the further development of molecular biology and neuroscience research in Western Australia and Australia. The use of neural stem cells holds therapeutic promise for the treatment of a wide variety of neurological conditions, including neurotrauma and stroke. The proposed research wil ....CX3C chemokine signalling in the olfactory epithelium and its role in the self regeneration of the olfactory system. The current proposal will explore new venues in adult neural stem cell research and contribute to the further development of molecular biology and neuroscience research in Western Australia and Australia. The use of neural stem cells holds therapeutic promise for the treatment of a wide variety of neurological conditions, including neurotrauma and stroke. The proposed research will provide new data on the fundamental cellular and molecular events that are required to trigger the birth, differentiation and conditions for growth of new neurons in the adult nervous system. The generation of such insights will be critical for any translational research.
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Understanding the molecular mechanisms regulating neuronal fusion. Neurons are tightly connected individual cells that communicate through chemical and electrical signals, and this project aims to discover the key molecules that allow these cells to remain as individual units without fusing with each other. The nervous system, unlike other tissues, is made of discrete individual cells, connected by chemical and electrical synapses but not by cytoplasmic continuity. However, how this is achieved ....Understanding the molecular mechanisms regulating neuronal fusion. Neurons are tightly connected individual cells that communicate through chemical and electrical signals, and this project aims to discover the key molecules that allow these cells to remain as individual units without fusing with each other. The nervous system, unlike other tissues, is made of discrete individual cells, connected by chemical and electrical synapses but not by cytoplasmic continuity. However, how this is achieved and how neurons maintain their individuality during development, remodelling and ageing is unknown. The project aims to address this gap using a genetic approach and the nematode Caenorhabditis elegans as an experimental system. The results may provide insights into how the nervous system develops and functions.Read moreRead less
Interactions between phenome and genome at developing CNS synapses during synaptic refinement. Activity-dependent changes in synaptic transmission are vital to development and function of central neuronal networks. However, the critical factors regulating developmental changes in synaptic signals remain largely unknown. We will correlate functional changes in synaptic responses at glutamate-releasing synapses with changes in glutamate receptor composition at a critical period during developmen ....Interactions between phenome and genome at developing CNS synapses during synaptic refinement. Activity-dependent changes in synaptic transmission are vital to development and function of central neuronal networks. However, the critical factors regulating developmental changes in synaptic signals remain largely unknown. We will correlate functional changes in synaptic responses at glutamate-releasing synapses with changes in glutamate receptor composition at a critical period during development, test whether synaptic activation of receptors is required for these changes and define the pattern of activity-dependent changes in gene expression necessary for developmental changes in synaptic transmission. Understanding this interaction between synaptic phenome and activity-dependent genomic expression will expand our understanding of brain development and function.Read moreRead less
Myofibroblast differentiation: from haemopoietic cells to smooth muscle. Until very recently the ability of adult cells with specific differentiated functions to re-differentiate for another function was thought to be extremely limited. However we have shown that cells ultimately derived from the bone marrow can differentiate into fibroblasts, then into myofibroblasts and then into smooth muscle cells. This project will build on these unique findings and determine the molecular mechanisms cont ....Myofibroblast differentiation: from haemopoietic cells to smooth muscle. Until very recently the ability of adult cells with specific differentiated functions to re-differentiate for another function was thought to be extremely limited. However we have shown that cells ultimately derived from the bone marrow can differentiate into fibroblasts, then into myofibroblasts and then into smooth muscle cells. This project will build on these unique findings and determine the molecular mechanisms controlling this process. We hypothesise that the local environment of a cell is critical and will involve a combination of particular extracellular matrix and growth factors as well as mechanical tension and the presence of other cell types.Read moreRead less
New guardians of the mucosa: Molecular characterisation of M cell biology. We aim to completely define the cellular and molecular biology of gut and lung M cells for the first time. We will elucidate how they develop, are regulated and function at a molecular level, and how M cells maintain normal gut and lung tissues and induce immune responses to protect against microbial challenges. In the future, the new insights will be essential pre-requisites for the development of mucosal-based intervent ....New guardians of the mucosa: Molecular characterisation of M cell biology. We aim to completely define the cellular and molecular biology of gut and lung M cells for the first time. We will elucidate how they develop, are regulated and function at a molecular level, and how M cells maintain normal gut and lung tissues and induce immune responses to protect against microbial challenges. In the future, the new insights will be essential pre-requisites for the development of mucosal-based interventions and vaccines that protect the gut and lung from infectious and inflammatory issues. The harnessing of effective immune responses to control such challenges, are of enormous fundamental and long-standing biological interest, and are amongst the most important areas of current scientific research.Read moreRead less
Assessing gene function in the developing brain using zebrafish as a model system. As the average life expectancy in western countries rises there is an increasing incidence of mental health problems. Therapeutic approaches to both Alzhemier's and Parkinson's disease, as well as to brain injury following stroke, rely on a thorough understanding of how the brain develops. This is consistent with the everyday principle that if you want to fix something that is broken, then you need to understand h ....Assessing gene function in the developing brain using zebrafish as a model system. As the average life expectancy in western countries rises there is an increasing incidence of mental health problems. Therapeutic approaches to both Alzhemier's and Parkinson's disease, as well as to brain injury following stroke, rely on a thorough understanding of how the brain develops. This is consistent with the everyday principle that if you want to fix something that is broken, then you need to understand how it is put together in the first place. This project seeks to understand how the normal brain is wired together in the embryo and, in doing so it will expose novel targets for therapy in the aged.Read moreRead less
Understanding how the multiple roles of olfactory ensheathing cells guide the growth and regeneration of olfactory axons. The outcomes of this project will increase the understanding of how nerve cells develop and regenerate after injury. The research outcomes and the development of new innovative methodologies as part of the project will be of high significance for the neuroscience research community both within Australia and overseas. The findings will also pave the way for the development of ....Understanding how the multiple roles of olfactory ensheathing cells guide the growth and regeneration of olfactory axons. The outcomes of this project will increase the understanding of how nerve cells develop and regenerate after injury. The research outcomes and the development of new innovative methodologies as part of the project will be of high significance for the neuroscience research community both within Australia and overseas. The findings will also pave the way for the development of novel therapies that promote neuronal regeneration relevant for disorders such as spinal cord injury and Alzheimer's disease, which constitute a large socio-economic burden in Australia. Currently, 400 people contract spinal cord injury every year, corresponding to an annual cost of $1 billion, and more than 500 000 aging people suffer from Alzheimer's disease.Read moreRead less
Development of novel reagents that specifically counteract EphA4 to enhance axonal regeneration. This project will examine the role of EphA4, an important guidance protein, in neural cell regeneration. The goal is to understand the signalling mechanisms that inhibit regeneration in the central nervous system and to develop novel biological agents to overcome these processes and promote functional recovery after nervous system injury or disease.
Click chemistry to reveal how neurons and glia shape perineuronal nets . The extracellular matrix (ECM) and its perineuronal nets (which are net-like structures with holes wrapped around neurons) are largely underexplored, despite representing a remarkable 20% of the brain’s total volume and having been suggested to be involved in many brain functions. Interestingly, digestion of the ECM improves learning and memory, but deficits return once the ECM has reformed. However, how this ECM remodellin ....Click chemistry to reveal how neurons and glia shape perineuronal nets . The extracellular matrix (ECM) and its perineuronal nets (which are net-like structures with holes wrapped around neurons) are largely underexplored, despite representing a remarkable 20% of the brain’s total volume and having been suggested to be involved in many brain functions. Interestingly, digestion of the ECM improves learning and memory, but deficits return once the ECM has reformed. However, how this ECM remodelling is organised at a cell-type level is not understood. Here we aim to close this knowledge gap, using cutting-edge technology including bioconjugation and ultrasound-mediated cargo delivery. Together, this project aims to contribute to a deeper understanding of this major brain compartment in neuronal function. Read moreRead less
Combined genetic and cellular analysis of melanisation to study variation in human pigmentation. This investigation examines variations in the genes that are important determinants of human skin pigmentation and are likely to be associated with skin cancer risk. Our research program will form the basis of future diagnostics based on major genes that determine a persons skin type. Current skin cancer prevention strategies rely predominantly on broad spectrum campaigns that are aimed at increasi ....Combined genetic and cellular analysis of melanisation to study variation in human pigmentation. This investigation examines variations in the genes that are important determinants of human skin pigmentation and are likely to be associated with skin cancer risk. Our research program will form the basis of future diagnostics based on major genes that determine a persons skin type. Current skin cancer prevention strategies rely predominantly on broad spectrum campaigns that are aimed at increasing the general community awareness of the damaging effects of UV radiation. A better understanding of the genetic basis of UV-sensitive skin types will greatly enhance the targeting of such skin cancer-prevention campaigns, provide an understanding of changes that occur in skin pathology, and the mechanisms of sun induced tanning.Read moreRead less