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
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
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
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
Defining novel immune checkpoints controlled by stromal cells. This project seeks to use innovative approaches to elucidate the mechanisms that define the earliest steps required to generate immune responses. The proposal builds on discoveries, including novel preliminary data, from a team with world-leading expertise in immunology, virology and stromal cell biology. The expected findings will provide fundamental insights into novel cellular and molecular interactions between stromal tissue comp ....Defining novel immune checkpoints controlled by stromal cells. This project seeks to use innovative approaches to elucidate the mechanisms that define the earliest steps required to generate immune responses. The proposal builds on discoveries, including novel preliminary data, from a team with world-leading expertise in immunology, virology and stromal cell biology. The expected findings will provide fundamental insights into novel cellular and molecular interactions between stromal tissue components and immune cells that initiate and regulate immune responses. Expected benefits include fundamental advances in knowledge, as well as insights that will ultimately benefit biotechnology and therapeutic applications, and in this way support research priorities linked to advanced manufacturing and health.
Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE230100084
Funder
Australian Research Council
Funding Amount
$471,754.00
Summary
Deciphering the rules of T cell residency across intestinal compartments. Tissue-resident memory T cells (TRM) are key for immune protection against infection and cancer at barrier sites including the gut. Whilst much of our understanding of gut TRM comes from studies on the small intestine, how these cells develop and function in the large intestine is unknown. Using state-of-the-art techniques and novel animal models, this project aims to (i) identify molecular pathways by which the local inte ....Deciphering the rules of T cell residency across intestinal compartments. Tissue-resident memory T cells (TRM) are key for immune protection against infection and cancer at barrier sites including the gut. Whilst much of our understanding of gut TRM comes from studies on the small intestine, how these cells develop and function in the large intestine is unknown. Using state-of-the-art techniques and novel animal models, this project aims to (i) identify molecular pathways by which the local intestinal microenvironment influences TRM development and (ii) how these pathways could modulate TRM generation specifically in the small or large intestine. The expected outcomes are to generate fundamental new knowledge that will have significance for regulation of the immune response. Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE240101101
Funder
Australian Research Council
Funding Amount
$452,077.00
Summary
Dissecting the heterogeniety of human tissue-resident memory T cells. Tissue-resident memory T cells (TRM) are key to immune protection against infection and cancer, yet dysfunctional TRM cause autoimmune disease. Whilst much of our understanding of TRM comes from animal models, how these cells work in humans is largely unknown. This project aims to define the phenotypic, functional and regulatory heterogeneity of human TRM subsets in organs like the gut, liver, and skin using a unique human org ....Dissecting the heterogeniety of human tissue-resident memory T cells. Tissue-resident memory T cells (TRM) are key to immune protection against infection and cancer, yet dysfunctional TRM cause autoimmune disease. Whilst much of our understanding of TRM comes from animal models, how these cells work in humans is largely unknown. This project aims to define the phenotypic, functional and regulatory heterogeneity of human TRM subsets in organs like the gut, liver, and skin using a unique human organ donor tissue resource. The expected outcomes are to generate fundamental new knowledge that will have significance for the development of new therapies against infectious diseases, cancer and autoimmunity.Read moreRead less