Defining the microenvironmental regulators of spleen function and immunity. The spleen is an important organ that is present in almost all vertebrates and is a critical site for the induction of systemic immune responses. The current paradigms of spleen biology are mostly derived from rodent studies, but the cellular biology of the spleen in humans remains poorly defined. Using novel tools, advanced transcriptomics and imaging techniques this project aims to reveal the functions of stromal cells ....Defining the microenvironmental regulators of spleen function and immunity. The spleen is an important organ that is present in almost all vertebrates and is a critical site for the induction of systemic immune responses. The current paradigms of spleen biology are mostly derived from rodent studies, but the cellular biology of the spleen in humans remains poorly defined. Using novel tools, advanced transcriptomics and imaging techniques this project aims to reveal the functions of stromal cells in the spleen in humans and to define the fundamental roles of spleen stromal cells in long-lived immunity. The anticipated outcomes are to build Australia’s research capacity and to generate new knowledge of significance for our fundamental understanding of the spleen and the role of this tissue in the immune system.Read moreRead less
Butyrophilin ligand sensing by the immune system. T cells are an important part of the immune system, surveying our body and preventing many diseases. A subset of T cells, gamma delta T cells, are a crucial component of the immune system. A key problem is that the mechanism(s) controlling gamma delta T cell behaviour are poorly understood. This proposal aims to decode how these cells are triggered into action by using innovative tools to investigate the molecular basis underpinning their functio ....Butyrophilin ligand sensing by the immune system. T cells are an important part of the immune system, surveying our body and preventing many diseases. A subset of T cells, gamma delta T cells, are a crucial component of the immune system. A key problem is that the mechanism(s) controlling gamma delta T cell behaviour are poorly understood. This proposal aims to decode how these cells are triggered into action by using innovative tools to investigate the molecular basis underpinning their function. This project expects to create fundamental new knowledge regarding how gamma-delta T cells are regulated, which will ultimately allow us to harness these cells to improve health.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
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
Human Leukocyte Antigen-A and -B regulation of Natural Killer cell function. The aim of this project is to determine how genetic variation in the genes encoding cell surface receptors expressed by innate lymphocytes and the molecules they recognise diversifies their capacity to sense and respond to infection. This knowledge is critical for understanding why there are intrinsic differences between individuals with respect to their capacity to respond to different types of infection and will ultim ....Human Leukocyte Antigen-A and -B regulation of Natural Killer cell function. The aim of this project is to determine how genetic variation in the genes encoding cell surface receptors expressed by innate lymphocytes and the molecules they recognise diversifies their capacity to sense and respond to infection. This knowledge is critical for understanding why there are intrinsic differences between individuals with respect to their capacity to respond to different types of infection and will ultimately inform our capacity to better deploy personalised medicines.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
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
Discovery Early Career Researcher Award - Grant ID: DE240100827
Funder
Australian Research Council
Funding Amount
$458,737.00
Summary
Delineating the developmental requirements for stem-like T cells. Stem-like CD8 T cells are critical for sustaining long-term systemic T cell activity. The signalling required for their development, however, remains elusive. Integrating multidisciplinary expertise, cutting-edge technology and highly innovative methods, this project aims to define the signalling cues provided by tissue microenvironment that control the development and maintenance of stem-like T cells, and thereby dictate systemic ....Delineating the developmental requirements for stem-like T cells. Stem-like CD8 T cells are critical for sustaining long-term systemic T cell activity. The signalling required for their development, however, remains elusive. Integrating multidisciplinary expertise, cutting-edge technology and highly innovative methods, this project aims to define the signalling cues provided by tissue microenvironment that control the development and maintenance of stem-like T cells, and thereby dictate systemic immunity. This project is expected to generate fundamental knowledge on basic immunology and T cell biology, which can benefit the academic, public health and biotechnology sectors by enhancing the international standing of Australian research on basic immunology and fostering new commercial opportunities. Read moreRead less
Redefining the immune landscape of the human ocular surface. At the ocular surface, the cornea and limbus need to mount effective immune responses to maintain corneal transparency for clear vision. The current paradigm is that the human cornea houses the same innate immune cell subsets (dendritic cells and macrophages) as naïve mice in pathogen-free facilities. Our pilot data challenge this premise, with early evidence that innate and adaptive cells (T cells) coexist in normal human corneas. Int ....Redefining the immune landscape of the human ocular surface. At the ocular surface, the cornea and limbus need to mount effective immune responses to maintain corneal transparency for clear vision. The current paradigm is that the human cornea houses the same innate immune cell subsets (dendritic cells and macrophages) as naïve mice in pathogen-free facilities. Our pilot data challenge this premise, with early evidence that innate and adaptive cells (T cells) coexist in normal human corneas. Integrating state-of-the-art techniques, we will advance understanding of immune regulation at the human ocular surface by comprehensively defining immune cell biology and dynamics. We will define the effect of age on immune cells in these tissues, and relationships between the tear proteome and cell behaviours.Read moreRead less