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How do unconventional T cells die? Mammalian cells die via several different mechanisms, each of which is tightly controlled at a molecular level. The choice of death pathway depends on the trigger and cell type. This project will investigate the mechanisms controlling death of T cells, including conventional T cells, and unconventional T cells, such as mucosal-associated invariant T (MAIT) cells, in normal conditions and during inflammation. It combines methods we developed to study MAIT cells ....How do unconventional T cells die? Mammalian cells die via several different mechanisms, each of which is tightly controlled at a molecular level. The choice of death pathway depends on the trigger and cell type. This project will investigate the mechanisms controlling death of T cells, including conventional T cells, and unconventional T cells, such as mucosal-associated invariant T (MAIT) cells, in normal conditions and during inflammation. It combines methods we developed to study MAIT cells in vivo with expertise in cell death analysis. This project is expected to elucidate the complex mechanisms controlling T cell survival/death and increase our fundamental understanding of cell death mechanisms of activated T cells.Read moreRead less
Pyroptotic macrophages posthumously sculpt immune responses. The life of an organism relies on the timely birth and death of its cells. Importantly, it is crucial for cells to die not only at the right time, but also in an appropriate manner. This proposal investigates a cell death pathway that triggers potent immune responses. This proposal seeks to reveal precisely how cell death sculpts immune responses. Expected outcomes include new insights into how immune cells die, and how they instruct i ....Pyroptotic macrophages posthumously sculpt immune responses. The life of an organism relies on the timely birth and death of its cells. Importantly, it is crucial for cells to die not only at the right time, but also in an appropriate manner. This proposal investigates a cell death pathway that triggers potent immune responses. This proposal seeks to reveal precisely how cell death sculpts immune responses. Expected outcomes include new insights into how immune cells die, and how they instruct immune responses from beyond the grave. Project benefits include a fundamental understanding of how cell death signalling sculpts tissue immune responses, and knowledge of how to manipulate cell death responses for future basic research and commercial applications beyond this project.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE240101286
Funder
Australian Research Council
Funding Amount
$469,707.00
Summary
SARS-CoV-2-induced dead cell fragments drive viral uptake and inflammation. This project will apply advanced cell biology and imaging techniques to investigate how macrophages, which lacks a canonical receptor for viral entry, become infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and elicit inflammatory responses. Its insights into a novel pathway of viral entry is expected to advance our understanding of host-pathogen interaction. The project is intended to uncover t ....SARS-CoV-2-induced dead cell fragments drive viral uptake and inflammation. This project will apply advanced cell biology and imaging techniques to investigate how macrophages, which lacks a canonical receptor for viral entry, become infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and elicit inflammatory responses. Its insights into a novel pathway of viral entry is expected to advance our understanding of host-pathogen interaction. The project is intended to uncover the role of SARS-CoV-2-induced dead cell fragmentation in promoting viral uptake and inflammation. Its findings should provide significant scientific, health and economic benefits by informing new research directions on infection and innate immunity as well as future therapeutic designs for infection treatment.Read moreRead less
Formation and clearance of endothelial cell-derived exophers. This project aims to investigate how cells that line the blood vessels release cellular wastes and their subsequent removal by immune cells.
It is critical that cellular waste are removed in a timely manner as their accumulation inside the cell can interfere with normal cell functions. The intended outcome of the project is to generate fundamental new knowledge of the mechanisms by which cellular waste are efficiently removed.
Exp ....Formation and clearance of endothelial cell-derived exophers. This project aims to investigate how cells that line the blood vessels release cellular wastes and their subsequent removal by immune cells.
It is critical that cellular waste are removed in a timely manner as their accumulation inside the cell can interfere with normal cell functions. The intended outcome of the project is to generate fundamental new knowledge of the mechanisms by which cellular waste are efficiently removed.
Expected outcomes encompass a paradigm-shift in understanding how cells that line the blood vessels dispose unwanted cellular contents. This should provide significant benefits including understanding how these specialised cells maintain the integrity of blood vessels and communicate with immune cells.Read moreRead less
Countdown to death: defining new signalling events preceding cell death . This proposal aims to understand how programmed cell death molecular machineries promote innate immune responses and proliferation by identifying new molecules that regulate these fundamental biological processes. This project expects to enhance our basic understanding of cell death, cell proliferation and innate immunity using innovative approaches and to build interdisciplinary collaborations. The new generated knowledge ....Countdown to death: defining new signalling events preceding cell death . This proposal aims to understand how programmed cell death molecular machineries promote innate immune responses and proliferation by identifying new molecules that regulate these fundamental biological processes. This project expects to enhance our basic understanding of cell death, cell proliferation and innate immunity using innovative approaches and to build interdisciplinary collaborations. The new generated knowledge in these critical processes will be fertile ground to develop innovative applications in biomedical industries. This this will have a positive impact on the health and economy of Australian society.Read moreRead less
Mapping the integration of T cell fate control across time and space. This project aims to apply new methods to determine how coordination of signalling complexes impacts upon the fate of cells of the adaptive immune system. It expects to determine how the context of signallng orchestrates cell fates such as differentiation, death and proliferation. The project is expected to yield an experimental and analytical platform for further investigations into a broad range of biological questions, and ....Mapping the integration of T cell fate control across time and space. This project aims to apply new methods to determine how coordination of signalling complexes impacts upon the fate of cells of the adaptive immune system. It expects to determine how the context of signallng orchestrates cell fates such as differentiation, death and proliferation. The project is expected to yield an experimental and analytical platform for further investigations into a broad range of biological questions, and to provide new knowledge of this fundamental problem. This platform should support further work that ultimately provides new models for tissue and immune cell regeneration, and new manufacturing platforms for therapies for humans and livestock, among other benefits.Read moreRead less
Transcriptional and translational regulation of the neuronal protein tau. The microtubule-associated protein tau is important for brain development and performance. To perform these functions, tau levels and its variants are tightly controlled in brain cells. However, the factors that regulate tau remain largely unknown. This project will employ latest gene technologies to identify the molecular regulators of tau, for each step of the process from DNA to the protein. The outcome of this study wi ....Transcriptional and translational regulation of the neuronal protein tau. The microtubule-associated protein tau is important for brain development and performance. To perform these functions, tau levels and its variants are tightly controlled in brain cells. However, the factors that regulate tau remain largely unknown. This project will employ latest gene technologies to identify the molecular regulators of tau, for each step of the process from DNA to the protein. The outcome of this study will significantly advance our understanding of gene regulation and mechanisms for controlling protein levels and contribute to a deeper understanding of brain function during development and aging.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE240100561
Funder
Australian Research Council
Funding Amount
$462,237.00
Summary
Understanding how platelets mediate new neuron formation in the adult brain. Exercise boosts the generation of new nerve cells from adult neural stem cells in the part of the brain responsible for learning and memory, the hippocampus. This project aims to investigate the mechanisms behind this effect, in particular, how blood cells known as platelets mediate this process. The expected outcomes include the discovery of new communication pathways between platelets and the brain following exercise ....Understanding how platelets mediate new neuron formation in the adult brain. Exercise boosts the generation of new nerve cells from adult neural stem cells in the part of the brain responsible for learning and memory, the hippocampus. This project aims to investigate the mechanisms behind this effect, in particular, how blood cells known as platelets mediate this process. The expected outcomes include the discovery of new communication pathways between platelets and the brain following exercise and will determine the importance of these blood cells in mediating brain function. This will help to explain how exercise affects the brain and may benefit Australian society through the implementation of new methods to support learning and memory in schools and workplaces, thereby enhancing performance and productivity.Read moreRead less
Defining how signalling pathways cooperate to regulate organ size. Control of organ size is essential for organ function and organism viability, and varies greatly across the animal kingdom. This project aims to understand how three important signalling pathways co-ordinately regulate organ size during development and also limit aberrant growth. By applying genomics, genetics and bioinformatics techniques, this project aims to discover a core set of growth genes that are regulated by different s ....Defining how signalling pathways cooperate to regulate organ size. Control of organ size is essential for organ function and organism viability, and varies greatly across the animal kingdom. This project aims to understand how three important signalling pathways co-ordinately regulate organ size during development and also limit aberrant growth. By applying genomics, genetics and bioinformatics techniques, this project aims to discover a core set of growth genes that are regulated by different signalling pathways and the mechanism by which transcription of these genes is repressed in order to eliminate faulty cells. Intended benefits are creation of jobs, new knowledge on fundamental principles of life and the stimulation of new research into organ size control.Read moreRead less
Understanding T cell trafficking and function during antigenic interference. Science generally studies antigenic stimulation in isolation, by measuring immunity towards antigens derived from a single pathogen. However, as mammals can harbour more than one infection at any given time, we established a model of antigenic interference using different antigens derived from two unrelated pathogens, influenza A (IAV) and Semliki Forest virus (SFV). Our data show that prior exposure to either IAV or SF ....Understanding T cell trafficking and function during antigenic interference. Science generally studies antigenic stimulation in isolation, by measuring immunity towards antigens derived from a single pathogen. However, as mammals can harbour more than one infection at any given time, we established a model of antigenic interference using different antigens derived from two unrelated pathogens, influenza A (IAV) and Semliki Forest virus (SFV). Our data show that prior exposure to either IAV or SFV greatly perturbs T cell dynamics. This proposal will study, at cellular and molecular levels, T cell trafficking, function and clonal distribution during antigenic interference, thus advance fundamental knowledge on T cell immunity during antigenic competition, and provide a new paradigm on how we research T cell immunity.Read moreRead less