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
Understanding the diverse biology of CD4+ T cell resident memory. This project aims to examine the biology of CD4 T cell memory in tissues. The previously unappreciated complexity of the CD4 T cell resident memory compartment in the liver will be characterised, focusing on the generation, maintenance and diversity of functions of these cells. Expected outcomes include the generation of fundamental knowledge in the disciplines of cellular biology and immunology, and unique, highly specialised stu ....Understanding the diverse biology of CD4+ T cell resident memory. This project aims to examine the biology of CD4 T cell memory in tissues. The previously unappreciated complexity of the CD4 T cell resident memory compartment in the liver will be characterised, focusing on the generation, maintenance and diversity of functions of these cells. Expected outcomes include the generation of fundamental knowledge in the disciplines of cellular biology and immunology, and unique, highly specialised student and personnel training through the interdisciplinary approach utilised, which spans cellular biology, live-imaging and transcriptomic analyses. Expected benefits include influential publications and the import of a novel, specialised technique to Australia through an international collaboration (Germany)Read moreRead less
How do unconventional T cells die? Mammalian cells die via several different mechanisms, each of which is tightly controlled at a molecular level. The choice of death pathway depends on the trigger and cell type. This project will investigate the mechanisms controlling death of T cells, including conventional T cells, and unconventional T cells, such as mucosal-associated invariant T (MAIT) cells, in normal conditions and during inflammation. It combines methods we developed to study MAIT cells ....How do unconventional T cells die? Mammalian cells die via several different mechanisms, each of which is tightly controlled at a molecular level. The choice of death pathway depends on the trigger and cell type. This project will investigate the mechanisms controlling death of T cells, including conventional T cells, and unconventional T cells, such as mucosal-associated invariant T (MAIT) cells, in normal conditions and during inflammation. It combines methods we developed to study MAIT cells in vivo with expertise in cell death analysis. This project is expected to elucidate the complex mechanisms controlling T cell survival/death and increase our fundamental understanding of cell death mechanisms of activated T cells.Read moreRead less
Defining pathways that control T cell lifespan for long-term immunity. This project will investigate the cellular and molecular pathways regulating lifespan of tissue-resident memory T cells (Trm cells), a non-circulating T cell subset that play a crucial role in the frontline defence against infection. Significantly, how long Trm cells live is paramount to how long immunity is sustained. Using cutting-edge cellular and molecular techniques, the expected outcomes of this project include identifi ....Defining pathways that control T cell lifespan for long-term immunity. This project will investigate the cellular and molecular pathways regulating lifespan of tissue-resident memory T cells (Trm cells), a non-circulating T cell subset that play a crucial role in the frontline defence against infection. Significantly, how long Trm cells live is paramount to how long immunity is sustained. Using cutting-edge cellular and molecular techniques, the expected outcomes of this project include identification of the genes and processes that control lifespan. This should provide significant benefits in the basic knowledge of how longevity of immunity is regulated. This understanding will be useful for future immunotherapeutic applications, such as veterinary or human vaccines requiring maximal duration of immunityRead moreRead less
Mapping the integration of T cell fate control across time and space. This project aims to apply new methods to determine how coordination of signalling complexes impacts upon the fate of cells of the adaptive immune system. It expects to determine how the context of signallng orchestrates cell fates such as differentiation, death and proliferation. The project is expected to yield an experimental and analytical platform for further investigations into a broad range of biological questions, and ....Mapping the integration of T cell fate control across time and space. This project aims to apply new methods to determine how coordination of signalling complexes impacts upon the fate of cells of the adaptive immune system. It expects to determine how the context of signallng orchestrates cell fates such as differentiation, death and proliferation. The project is expected to yield an experimental and analytical platform for further investigations into a broad range of biological questions, and to provide new knowledge of this fundamental problem. This platform should support further work that ultimately provides new models for tissue and immune cell regeneration, and new manufacturing platforms for therapies for humans and livestock, among other benefits.Read moreRead less
Understanding T cell trafficking and function during antigenic interference. Science generally studies antigenic stimulation in isolation, by measuring immunity towards antigens derived from a single pathogen. However, as mammals can harbour more than one infection at any given time, we established a model of antigenic interference using different antigens derived from two unrelated pathogens, influenza A (IAV) and Semliki Forest virus (SFV). Our data show that prior exposure to either IAV or SF ....Understanding T cell trafficking and function during antigenic interference. Science generally studies antigenic stimulation in isolation, by measuring immunity towards antigens derived from a single pathogen. However, as mammals can harbour more than one infection at any given time, we established a model of antigenic interference using different antigens derived from two unrelated pathogens, influenza A (IAV) and Semliki Forest virus (SFV). Our data show that prior exposure to either IAV or SFV greatly perturbs T cell dynamics. This proposal will study, at cellular and molecular levels, T cell trafficking, function and clonal distribution during antigenic interference, thus advance fundamental knowledge on T cell immunity during antigenic competition, and provide a new paradigm on how we research T cell immunity.Read moreRead less
Understanding the life and death of Mucosal-associated invariant T cells. Cell death of naïve T cells in lymphoid organs is well-understood. However, T cells only gain their function upon activation, and how activated T cells regulate their life or death remains unclear. Mucosal-associated Invariant T (MAIT) cells are abundant in non-lymphoid tissues as key local players in immunity, and share some features of activated conventional T cells. This project aims to define how MAIT cell survival and ....Understanding the life and death of Mucosal-associated invariant T cells. Cell death of naïve T cells in lymphoid organs is well-understood. However, T cells only gain their function upon activation, and how activated T cells regulate their life or death remains unclear. Mucosal-associated Invariant T (MAIT) cells are abundant in non-lymphoid tissues as key local players in immunity, and share some features of activated conventional T cells. This project aims to define how MAIT cell survival and death are controlled. It combines methods we developed to track MAIT cells in vivo with expertise in cell death analysis. This project is expected to elucidate the complex mechanisms controlling MAIT cell survival/death and increase our fundamental understanding of cell death mechanisms of activated T cells.Read moreRead less
Understanding how the heart becomes more efficient. The body demands that the heart function at utmost efficiency. Trabeculae – folds within the heart lumen – maximise blood flow, contribute to chamber development and form the electrical conduction network of the heart. Problems with trabeculae formation cause cardiomyopathy and arrhythmia and yet we do not understand its basic development. The project will investigate the earliest stages of when this tissue develops its identity and examine the ....Understanding how the heart becomes more efficient. The body demands that the heart function at utmost efficiency. Trabeculae – folds within the heart lumen – maximise blood flow, contribute to chamber development and form the electrical conduction network of the heart. Problems with trabeculae formation cause cardiomyopathy and arrhythmia and yet we do not understand its basic development. The project will investigate the earliest stages of when this tissue develops its identity and examine the signalling, genetic, cellular and extracellular cues required to instruct trabeculae to form in the heart. Findings from this research will revise our understanding of when and how trabeculae form and provide key information about how to grow and repair this important tissue.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
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