Microtubule structure in nervous system repair. This Project aims to investigate the role of structural and functional cellular components known as microtubules in nervous system regeneration. This Project aims to use innovative approaches in confocal and electron microscopy, genetics, and cell biology, with the expectation of generating new knowledge into nervous system repair. Expected outcomes of this Project include a comprehensive description of how microtubules are rearranged following ner ....Microtubule structure in nervous system repair. This Project aims to investigate the role of structural and functional cellular components known as microtubules in nervous system regeneration. This Project aims to use innovative approaches in confocal and electron microscopy, genetics, and cell biology, with the expectation of generating new knowledge into nervous system repair. Expected outcomes of this Project include a comprehensive description of how microtubules are rearranged following nervous system injury and the importance of microtubule modifying proteins in promoting regeneration. This should provide significant benefits in our understanding of the cellular mechanisms behind nervous system repair, and offer new approaches for promoting regeneration after injury.Read moreRead less
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
The molecular basis of T cell receptor cross-reactivity between MHC and MR1. This project aims to investigate how newly discovered immune cells, known as 'MR1T' cells, function in the body. Preliminary evidence shows that MR1T cells can kill stressed cells. This project expects to generate new knowledge describing precisely how MR1T cells target and kill stressed cells. Expected outcomes of this project include to refine research techniques and models, foster interinstitutional collaborations, a ....The molecular basis of T cell receptor cross-reactivity between MHC and MR1. This project aims to investigate how newly discovered immune cells, known as 'MR1T' cells, function in the body. Preliminary evidence shows that MR1T cells can kill stressed cells. This project expects to generate new knowledge describing precisely how MR1T cells target and kill stressed cells. Expected outcomes of this project include to refine research techniques and models, foster interinstitutional collaborations, and further develop our theory on MR1T cell function. This project should provide significant benefits, such as publication of research articles in high impact journals and generation of experimental tools sought after by researchers in the field.Read moreRead less
Deciphering the immune complexity that orchestrates T cell activation. The adaptive immune system consists of a complex cellular network that can efficiently distinguish exogenous required inputs, such as nutrients, from those that are potentially harmful like pathogens. Such ‘friend-foe’ discrimination has its molecular basis in a multitude of receptors with specificity to certain ligands. Critically, however, it is unclear how such discrimination is mechanistically regulated at the functional ....Deciphering the immune complexity that orchestrates T cell activation. The adaptive immune system consists of a complex cellular network that can efficiently distinguish exogenous required inputs, such as nutrients, from those that are potentially harmful like pathogens. Such ‘friend-foe’ discrimination has its molecular basis in a multitude of receptors with specificity to certain ligands. Critically, however, it is unclear how such discrimination is mechanistically regulated at the functional level. We have developed new and sophisticated experimental models that will allow us to systematically dissect and unfold the complexity of the adaptive immune system and address this critical knowledge gap. Expected outcomes will critically advance our general understanding of a fundamental biological principle.Read moreRead less
Whole-body analysis of human tissue-resident memory T cells. T cells provide critical immune protection against infection and cancer, and dysfunctional T cells cause autoimmune disease. Much of our understanding of T cells comes from studies of mice and how these immune cells work in humans is not fully understood. This project aims to determine how human T cells persist and function using a unique organ donor tissue resource. The expected outcomes are to generate fundamental new knowledge about ....Whole-body analysis of human tissue-resident memory T cells. T cells provide critical immune protection against infection and cancer, and dysfunctional T cells cause autoimmune disease. Much of our understanding of T cells comes from studies of mice and how these immune cells work in humans is not fully understood. This project aims to determine how human T cells persist and function using a unique organ donor tissue resource. The expected outcomes are to generate fundamental new knowledge about the regulation of the human immune response. This knowledge is critical for the development of vaccines and immunotherapies designed to harness T cell immunity.Read moreRead less
Electrical properties of human dendrites. This project aims to determine the electrical properties of dendrites in human neurons. Dendrites are the primary site of synaptic input to neurons and their electrical properties play a key role in information processing in the brain. While we know much about the electrical properties of dendrites in other species, primarily rodents, little is known about the electrical properties of human dendrites. This project aims to address this gap in knowledge fo ....Electrical properties of human dendrites. This project aims to determine the electrical properties of dendrites in human neurons. Dendrites are the primary site of synaptic input to neurons and their electrical properties play a key role in information processing in the brain. While we know much about the electrical properties of dendrites in other species, primarily rodents, little is known about the electrical properties of human dendrites. This project aims to address this gap in knowledge for the first time. The results obtained will shed light on the mechanisms the brain uses to process information, and therefore will bring us a step closer to truly understanding ourselves.Read moreRead less
CD1C-LIPID-REACTIVE T CELLS. The immune system patrols our body examining molecules such as proteins and lipids that signal whether or not everything is ok. While protein recognition by the immune system is well understood, our knowledge of the fundamental features of lipid detection is poor. This project will investigate the detection of lipid molecules that are presented to the immune system in association with a molecule known as CD1c. The aims are to understand: 1. The cells that respond to ....CD1C-LIPID-REACTIVE T CELLS. The immune system patrols our body examining molecules such as proteins and lipids that signal whether or not everything is ok. While protein recognition by the immune system is well understood, our knowledge of the fundamental features of lipid detection is poor. This project will investigate the detection of lipid molecules that are presented to the immune system in association with a molecule known as CD1c. The aims are to understand: 1. The cells that respond to these lipids; 2. The cellular receptors that bind to these lipids; 3. The types of lipids involved in this process. This work is essential for us to understand lipid-based immunology which is critical if we ultimately wish to harness this to improve human health.Read moreRead less
Intraepithelial lymphocyte development and function in the intestine. This study aims to better understand the homeostatic maintenance and essential repair processes in the intestine. This project will generate new knowledge of how immune cells of the intestine, known as intraepithelial lymphocytes (IELs), engage with intestinal epithelial cells, neurons and commensal microbes to promote homeostasis and repair. Expected outcomes of this project will be identification of new molecules for future ....Intraepithelial lymphocyte development and function in the intestine. This study aims to better understand the homeostatic maintenance and essential repair processes in the intestine. This project will generate new knowledge of how immune cells of the intestine, known as intraepithelial lymphocytes (IELs), engage with intestinal epithelial cells, neurons and commensal microbes to promote homeostasis and repair. Expected outcomes of this project will be identification of new molecules for future drug and vaccine development to improve gut health and vaccination in mammals. This should provide significant benefits to the Australian population and livestock industry through improved protection against cancer, intestinal infections and increased productivity. Read moreRead less
Novel role of RNA methylation in neuronal homeostasis. This proposal is aimed at understanding the RNA signalling that takes place in neuronal homeostatic response. The crucial role of neuronal homeostasis for normal brain function is evidenced throughout the nervous system; however, the precise underlying mechanisms are still not well understood. The proposed research will utilise high-throughput sequencing approaches coupled with biochemical, molecular and cell biological assays to provide mec ....Novel role of RNA methylation in neuronal homeostasis. This proposal is aimed at understanding the RNA signalling that takes place in neuronal homeostatic response. The crucial role of neuronal homeostasis for normal brain function is evidenced throughout the nervous system; however, the precise underlying mechanisms are still not well understood. The proposed research will utilise high-throughput sequencing approaches coupled with biochemical, molecular and cell biological assays to provide mechanistic insights into the molecular processes that control neuronal homeostatic responses. This will elucidate how neural plasticity and network stability are maintained, a process that is critical for our understanding of sensory processing, learning and memory throughout life.Read moreRead less
Old brain cells perform new tricks to allow life-long learning. In the brain, nerve cells transmit electrical signals more quickly and reliably when they are insulated. The insulating cells undergo small adaptive changes that speed up information transfer during learning, and the faster the electrical signal, the better the learning outcomes. This project aims to understand the signals that direct insulating cells to adapt and support life-long learning. In the longer term, this knowledge may be ....Old brain cells perform new tricks to allow life-long learning. In the brain, nerve cells transmit electrical signals more quickly and reliably when they are insulated. The insulating cells undergo small adaptive changes that speed up information transfer during learning, and the faster the electrical signal, the better the learning outcomes. This project aims to understand the signals that direct insulating cells to adapt and support life-long learning. In the longer term, this knowledge may be used to: develop interventions that improve learning and educational outcomes; counteract age-related memory decline and enable longer work force participation; develop strategies to circumvent the memory loss caused by brain diseases, or improve the design of computer hardware.Read moreRead less