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: DE220100185
Funder
Australian Research Council
Funding Amount
$438,712.00
Summary
Decoding the evolution of killer T cell immunity across human lifetime. The immune system is a potent weapon for protection against pathogens. T cells have a central role as their receptors monitor the body for threats. The thymus (organ) educates receptors to discriminate between healthy and infected cells. Receptor diversity and T cell strength change throughout human life. This project aims to unravel how T cells gain and lose optimal receptors and strength. The aims are to understand 1) The ....Decoding the evolution of killer T cell immunity across human lifetime. The immune system is a potent weapon for protection against pathogens. T cells have a central role as their receptors monitor the body for threats. The thymus (organ) educates receptors to discriminate between healthy and infected cells. Receptor diversity and T cell strength change throughout human life. This project aims to unravel how T cells gain and lose optimal receptors and strength. The aims are to understand 1) The role of thymic education in diversifying receptors 2) Whether gradual loss of thymic education affects receptor diversity 3) The molecular mechanisms underlying T cell strength. The project is essential for understanding how optimal T cell immunity is formed, critical if we wish to harness this to improve healthy aging.Read moreRead less
Marine sponge–microbe interactions and the origin of animal innate immunity. This project aims to address how the animal innate immune system evolved to discriminate between potential pathogens versus beneficial symbionts by studying a marine sponge holobiont. Using advanced genomic and cellular approaches, the project will uncover deeply conserved regulatory pathways used by the cells of sponges, humans and other animals, and thereby identify cardinal rules governing animal innate immunity and ....Marine sponge–microbe interactions and the origin of animal innate immunity. This project aims to address how the animal innate immune system evolved to discriminate between potential pathogens versus beneficial symbionts by studying a marine sponge holobiont. Using advanced genomic and cellular approaches, the project will uncover deeply conserved regulatory pathways used by the cells of sponges, humans and other animals, and thereby identify cardinal rules governing animal innate immunity and its evolutionary origin. The project will provide an understanding of how beneficial microbial symbionts are recruited and maintained by animals, and are instrumental to the health of our environment and all its inhabitants.Read moreRead less
CD1C-LIPID-REACTIVE T CELLS. The immune system patrols our body examining molecules such as proteins and lipids that signal whether or not everything is ok. While protein recognition by the immune system is well understood, our knowledge of the fundamental features of lipid detection is poor. This project will investigate the detection of lipid molecules that are presented to the immune system in association with a molecule known as CD1c. The aims are to understand: 1. The cells that respond to ....CD1C-LIPID-REACTIVE T CELLS. The immune system patrols our body examining molecules such as proteins and lipids that signal whether or not everything is ok. While protein recognition by the immune system is well understood, our knowledge of the fundamental features of lipid detection is poor. This project will investigate the detection of lipid molecules that are presented to the immune system in association with a molecule known as CD1c. The aims are to understand: 1. The cells that respond to these lipids; 2. The cellular receptors that bind to these lipids; 3. The types of lipids involved in this process. This work is essential for us to understand lipid-based immunology which is critical if we ultimately wish to harness this to improve human health.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
Development of an immunology toolbox to combat emerging marsupial diseases. Disease is increasingly a driver of wildlife population declines in Australia. However, basic immunology tools for >99% of vertebrate species are scarce, limiting our ability to prevent and respond to emerging and endemic diseases, such as devil facial tumour disease and wobbly possum disease. The overarching goal of this project is to improve wildlife health and fill the marsupial immunology gap by developing a long-ove ....Development of an immunology toolbox to combat emerging marsupial diseases. Disease is increasingly a driver of wildlife population declines in Australia. However, basic immunology tools for >99% of vertebrate species are scarce, limiting our ability to prevent and respond to emerging and endemic diseases, such as devil facial tumour disease and wobbly possum disease. The overarching goal of this project is to improve wildlife health and fill the marsupial immunology gap by developing a long-overdue multispecies marsupial immunology toolbox. The toolbox is needed to accelerate devil facial tumour disease vaccine progress and conservation immunology research. It will expand our knowledge of wobbly possum disease virus that is increasingly reported in Tasmania and the risk posed by the virus to other possum species.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