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
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
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: LE210100001
Funder
Australian Research Council
Funding Amount
$875,000.00
Summary
A 3-photon imaging system for deep live imaging. This project aims to establish Australia’s first 3-photon microscope system with adaptive optics for deep intravital imaging. This advanced imaging system will enable researchers to investigate the biology of cells and tissue structures in a wide range of organs and engineered tissues, to a degree not possible with existing technology. This project will capitalise on advanced laser, microscope and adaptive optics technologies with the expected out ....A 3-photon imaging system for deep live imaging. This project aims to establish Australia’s first 3-photon microscope system with adaptive optics for deep intravital imaging. This advanced imaging system will enable researchers to investigate the biology of cells and tissue structures in a wide range of organs and engineered tissues, to a degree not possible with existing technology. This project will capitalise on advanced laser, microscope and adaptive optics technologies with the expected outcomes to include the generation of new knowledge of major biological systems, including the immune system and the nervous system. This will provide significant benefits to fundamental interdisciplinary research into immunology, infectious disease, neuroscience, mechanobiology and engineering.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
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE110100092
Funder
Australian Research Council
Funding Amount
$300,000.00
Summary
Fluorescence microscopy with optical tweezers: imaging cellular responses. Life relies on the ability of our cells to receive and respond to signals with pinpoint accuracy, involving both chemical and mechanical signals. This equipment will allow scientists to expose cells to both types of signals and measure the response at an unprecedented level of accuracy for the first time.
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
Understanding T cell immunity induced by infection. We aim to understand how killer T cells are “programmed” upon activation and acquire their characteristic functions and how these are maintained into immunological memory. This proposal will provide insights important for the design and improvement of vaccine strategies to fight pathogens such as influenza, HIV and even tumors.