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
Regulation of lung immune-epithelial networks sensing environmental change. This study aims to uncover how lung epithelial cells engage with immune cells and determine their cellular and molecular wiring to ensure homeostatic maintenance and essential repair processes of lung tissues. Maintenance of lung epithelial-immune networks is essential to maintain normal lung tissue structure and function, and to induce immune responses to protect against microbial challenges or inhaled potentially toxic ....Regulation of lung immune-epithelial networks sensing environmental change. This study aims to uncover how lung epithelial cells engage with immune cells and determine their cellular and molecular wiring to ensure homeostatic maintenance and essential repair processes of lung tissues. Maintenance of lung epithelial-immune networks is essential to maintain normal lung tissue structure and function, and to induce immune responses to protect against microbial challenges or inhaled potentially toxic substances. Understanding this molecular program of epithelial-immune cell-mediated sensing/repair will be essential to understand how tissue-repair processes can be driven in the lung, an organ critical for respiration and thus life.Read moreRead less
An investigation into CD1a, a versatile antigen-presenting molecule. This project aims to investigate how T lymphocytes are activated by lipids presented by the skin-associated antigen-presenting molecule, CD1a. Using X-ray crystallography and cellular immunology, we will provide fundamental insight into this poorly understood immunological axis. We will determine the molecular basis for how CD1a presents diverse self and foreign lipids, and how such CD1a-lipid complexes are recognised by the r ....An investigation into CD1a, a versatile antigen-presenting molecule. This project aims to investigate how T lymphocytes are activated by lipids presented by the skin-associated antigen-presenting molecule, CD1a. Using X-ray crystallography and cellular immunology, we will provide fundamental insight into this poorly understood immunological axis. We will determine the molecular basis for how CD1a presents diverse self and foreign lipids, and how such CD1a-lipid complexes are recognised by the responding T cells. This basic science discovery project will provide substantial new knowledge in the burgeoning field of lipid-mediated immunity, which should ultimately lead to new therapies targeting the CD1a lipid display molecule to either prevent immune mediated damage or promote protective immunity as required.Read moreRead less
A novel axis of cooperation between innate and adaptive immunity. The project aims to understand how two molecular components of the immune system, Complement and MHC, cooperate to protect the host. Further, these two molecules mediate trogocytosis, a little-studied form of intercellular communication, between two major immune cell types: dendritic cells and B cells. The project will be multidisciplinary, applying high-end microscopy, biochemistry, cell biology and immunology techniques. Person ....A novel axis of cooperation between innate and adaptive immunity. The project aims to understand how two molecular components of the immune system, Complement and MHC, cooperate to protect the host. Further, these two molecules mediate trogocytosis, a little-studied form of intercellular communication, between two major immune cell types: dendritic cells and B cells. The project will be multidisciplinary, applying high-end microscopy, biochemistry, cell biology and immunology techniques. Personnel will be trained in cutting-edge techniques. The project will expand knowledge on basic immunology and cell-cell cooperation. It will generate intellectual property for the biotechnology sector to develop new commercial products that might improve the health of humans and also animals of economic importance.Read moreRead less
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
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
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
Molecular determinants of an allergic response. Some humans develop allergies after exposure to environmental allergens while others do not. At present, the reason for this individual variation is not known. By comparing the processes activated in allergic versus non-allergic individuals, this study will identify critical molecules involved in making individuals susceptible to allergies, which will be used to develop safer and more effective allergy vaccines.
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