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
Discovery Early Career Researcher Award - Grant ID: DE220100165
Funder
Australian Research Council
Funding Amount
$451,900.00
Summary
Engineering T cells to promote peripheral immunity. Tissue-resident memory T cells (TRM) are key for immune protection against infections and cancer. This has led to much interest in understanding how these immune cells develop, although elucidation of molecules that regulate TRM are still scarce. This project aims to (i) identify genetic drivers of TRM in peripheral organs and (ii) modulate TRM generation utilising state-of-the-art genetic engineering techniques. Expected outcomes include gener ....Engineering T cells to promote peripheral immunity. Tissue-resident memory T cells (TRM) are key for immune protection against infections and cancer. This has led to much interest in understanding how these immune cells develop, although elucidation of molecules that regulate TRM are still scarce. This project aims to (i) identify genetic drivers of TRM in peripheral organs and (ii) modulate TRM generation utilising state-of-the-art genetic engineering techniques. Expected outcomes include generating new knowledge that will contribute to the development of novel therapeutics against infectious disease and cancer, together with the benefit of promoting national and international collaboration with the ultimate goal of improving health.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
Discovery Early Career Researcher Award - Grant ID: DE200101300
Funder
Australian Research Council
Funding Amount
$423,711.00
Summary
Lipopolysaccharide-induced macrophage extracellular traps in host defence. The innate immune system is the first line of defence against invading microbes. Macrophages are key innate immune cells that deploy antimicrobial responses to clear infection and restore health. There are many critical unanswered questions on the molecular mechanisms that drive macrophage inflammatory and antimicrobial pathways. This project aims to elucidate a novel inflammatory mechanism that immobilises and kills inva ....Lipopolysaccharide-induced macrophage extracellular traps in host defence. The innate immune system is the first line of defence against invading microbes. Macrophages are key innate immune cells that deploy antimicrobial responses to clear infection and restore health. There are many critical unanswered questions on the molecular mechanisms that drive macrophage inflammatory and antimicrobial pathways. This project aims to elucidate a novel inflammatory mechanism that immobilises and kills invading bacteria via newly discovered structures made by dying macrophages called extracellular traps. Insight we gain by interrogating this immune cell signalling pathway, called the non-canonical inflammasome, will add valuable knowledge to our fundamental understanding of mammalian inflammation and anti-microbial responses
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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