Understanding the diverse biology of CD4+ T cell resident memory. This project aims to examine the biology of CD4 T cell memory in tissues. The previously unappreciated complexity of the CD4 T cell resident memory compartment in the liver will be characterised, focusing on the generation, maintenance and diversity of functions of these cells. Expected outcomes include the generation of fundamental knowledge in the disciplines of cellular biology and immunology, and unique, highly specialised stu ....Understanding the diverse biology of CD4+ T cell resident memory. This project aims to examine the biology of CD4 T cell memory in tissues. The previously unappreciated complexity of the CD4 T cell resident memory compartment in the liver will be characterised, focusing on the generation, maintenance and diversity of functions of these cells. Expected outcomes include the generation of fundamental knowledge in the disciplines of cellular biology and immunology, and unique, highly specialised student and personnel training through the interdisciplinary approach utilised, which spans cellular biology, live-imaging and transcriptomic analyses. Expected benefits include influential publications and the import of a novel, specialised technique to Australia through an international collaboration (Germany)Read moreRead less
A cellular hub for the organisation of T cell priming. This project aims to delineate the cellular interactions involved in the initiation of immune responses by utilising advanced in vivo imaging. Adaptive immunity in vertebrates functions via the acquisition of signals by immune cells via complex interactions with other immune cells, yet these exchanges are difficult to observe and define. This project expects to provide insights into the mechanisms that underpin effective cell-mediated immune ....A cellular hub for the organisation of T cell priming. This project aims to delineate the cellular interactions involved in the initiation of immune responses by utilising advanced in vivo imaging. Adaptive immunity in vertebrates functions via the acquisition of signals by immune cells via complex interactions with other immune cells, yet these exchanges are difficult to observe and define. This project expects to provide insights into the mechanisms that underpin effective cell-mediated immune responses. The expected outcomes are to generate fundamental new knowledge about immune responses and enhance capacity to study the immune system. This could benefit future development of new vaccines and therapies to improve health.Read moreRead less
Defining the immunological roles of stromal cells within lymphoid tissues. The populations of endothelial and mesenchymal cells that construct the lymphoid tissues are being revealed as key players in the priming and orchestration of immune responses. Yet, fundamental knowledge of the molecular makeup and the functions of these stromal cells, particularly their roles in immune responses, is sorely lacking. This project will utilise a multidisciplinary approach including advanced imaging and bioi ....Defining the immunological roles of stromal cells within lymphoid tissues. The populations of endothelial and mesenchymal cells that construct the lymphoid tissues are being revealed as key players in the priming and orchestration of immune responses. Yet, fundamental knowledge of the molecular makeup and the functions of these stromal cells, particularly their roles in immune responses, is sorely lacking. This project will utilise a multidisciplinary approach including advanced imaging and bioinformatics to dissect the functions of the lymphoid stromal cells and their roles in the swelling of lymphoid tissues during immune responses. This will provide vital information about the biology of these understudied cells and reveal the ways in which they support the generation of immunity.Read moreRead less
Imaging the generation and recall of protective antiviral immune responses in vivo. Our understanding of the in vivo dynamics of cellular immune responses to infectious diseases is poor. This project will utilise advanced intravital imaging combined with novel tools to dissect the cellular events involved in the generation and recall of T cell responses to localised virus infection, combined with a detailed functional analysis of the lymphoid organ stroma. Such fundamental information will contr ....Imaging the generation and recall of protective antiviral immune responses in vivo. Our understanding of the in vivo dynamics of cellular immune responses to infectious diseases is poor. This project will utilise advanced intravital imaging combined with novel tools to dissect the cellular events involved in the generation and recall of T cell responses to localised virus infection, combined with a detailed functional analysis of the lymphoid organ stroma. Such fundamental information will contribute to the development of new generation vaccines and therapies to protect against tissue-specific infectious diseases, cancers and autoimmune diseases.Read moreRead less
Sphingosine-1-phosphate receptor 5: a novel regulator of T cell immunity. T cells provide critical immune protection against infection and cancer. However, the pathways that regulate these immune cells are not fully understood. T cells express a molecule called S1P5 that has an unknown function in these cells. In this proposal, we reveal new evidence that this molecule is an unappreciated and crucial regulator of T cell behaviour. Using state-of-the-art techniques and novel genetic tools, this p ....Sphingosine-1-phosphate receptor 5: a novel regulator of T cell immunity. T cells provide critical immune protection against infection and cancer. However, the pathways that regulate these immune cells are not fully understood. T cells express a molecule called S1P5 that has an unknown function in these cells. In this proposal, we reveal new evidence that this molecule is an unappreciated and crucial regulator of T cell behaviour. Using state-of-the-art techniques and novel genetic tools, this project aims to discover the involvement of S1P5 in the immune response, and determine how S1P5 can be controlled to enhance protective T cell immunity. The expected outcomes are to generate fundamental new knowledge that will have significance for regulation of the immune response. Read moreRead less
New guardians of the mucosa: Molecular characterisation of M cell biology. We aim to completely define the cellular and molecular biology of gut and lung M cells for the first time. We will elucidate how they develop, are regulated and function at a molecular level, and how M cells maintain normal gut and lung tissues and induce immune responses to protect against microbial challenges. In the future, the new insights will be essential pre-requisites for the development of mucosal-based intervent ....New guardians of the mucosa: Molecular characterisation of M cell biology. We aim to completely define the cellular and molecular biology of gut and lung M cells for the first time. We will elucidate how they develop, are regulated and function at a molecular level, and how M cells maintain normal gut and lung tissues and induce immune responses to protect against microbial challenges. In the future, the new insights will be essential pre-requisites for the development of mucosal-based interventions and vaccines that protect the gut and lung from infectious and inflammatory issues. The harnessing of effective immune responses to control such challenges, are of enormous fundamental and long-standing biological interest, and are amongst the most important areas of current scientific research.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE170100226
Funder
Australian Research Council
Funding Amount
$372,000.00
Summary
How innate lymphoid cells regulate mammalian lung development. This project aims to determine the ability of a subset of lung resident immune cells to promote normal lung development through the regulation of stem cells. The lung is constantly exposed to countless environmental challenges including microbes. Mammals’ local immune systems protect the lung from these challenges. This is particularly important in early-life when the lung is still developing. However, impaired lung development affec ....How innate lymphoid cells regulate mammalian lung development. This project aims to determine the ability of a subset of lung resident immune cells to promote normal lung development through the regulation of stem cells. The lung is constantly exposed to countless environmental challenges including microbes. Mammals’ local immune systems protect the lung from these challenges. This is particularly important in early-life when the lung is still developing. However, impaired lung development affects humans and livestock, costing >$3 billion p.a. The intended outcome is to identify basic biological processes involved in normal mammalian lung development, which may lead to strategies to prevent chronic lung diseases in humans and animals.Read moreRead less
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
Discovery Early Career Researcher Award - Grant ID: DE220100830
Funder
Australian Research Council
Funding Amount
$464,928.00
Summary
Elucidating the genesis of MAIT cell-mediated immunity. T cells develop in the thymus and proceed to survey our body probing molecules that signal if anything is abnormal. A specialised subset of T cells, mucosal associated invariant T (MAIT) cells are crucial in detecting microbial molecules and infection, yet their numbers vary widely between individuals. A key problem is that the factors controlling their development and function are poorly understood. This proposal aims to decode this critic ....Elucidating the genesis of MAIT cell-mediated immunity. T cells develop in the thymus and proceed to survey our body probing molecules that signal if anything is abnormal. A specialised subset of T cells, mucosal associated invariant T (MAIT) cells are crucial in detecting microbial molecules and infection, yet their numbers vary widely between individuals. A key problem is that the factors controlling their development and function are poorly understood. This proposal aims to decode this critical issue in MAIT cell biology, using innovative tools to investigate the molecular basis underpinning their development in the thymus. This work will provide vital, fundamental discoveries into how MAIT cells are produced and regulated, as we ultimately wish to harness MAIT cells to improve human health. Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE140100149
Funder
Australian Research Council
Funding Amount
$300,000.00
Summary
CyTOF platform for the Advanced Cytometry Facility: overcoming fluorescence spectral barriers to truly multiparametric cytometry by mass spectrometry. Cytometry by time-of-flight mass spectrometry platform for the Advanced Cytometry Facility: overcoming fluorescence spectral barriers to truly multiparametric cytometry by mass spectrometry: This project will provide a flow cytometer capable of analysing single cells by time-of-flight mass spectrometry. Antibody labels for cell components will ena ....CyTOF platform for the Advanced Cytometry Facility: overcoming fluorescence spectral barriers to truly multiparametric cytometry by mass spectrometry. Cytometry by time-of-flight mass spectrometry platform for the Advanced Cytometry Facility: overcoming fluorescence spectral barriers to truly multiparametric cytometry by mass spectrometry: This project will provide a flow cytometer capable of analysing single cells by time-of-flight mass spectrometry. Antibody labels for cell components will enable measurement of up to 100 parameters/cell. Developing analytical and modelling algorithms like Spanning tree Progression of Density normalised Events (SPADE), this project will aim to map the relationships of various unelucidated cell lineages, via functional pathway connections. New pathways thus revealed will enable elaboration and use of novel specific molecules in perturbational analyses to confirm and further enhance the understanding of these highly intricate, basic relationships. This will provide unparalleled insight, both into early development of stem cells and mechanisms of maintenance of homeostasis in differentiated cells.Read moreRead less