Unrestricted antigen recognition by T lymphocytes. This project aims to investigate the unrestricted T cell repertoire; the molecular and structural basis of antigen recognition by unrestricted T cells; and the development of unrestricted T cells. T lymphocytes typically are restricted to detecting foreign molecules (antigens) on the cell membrane in association with specialised antigen-presenting molecules encoded within the highly polymorphic major histocompatibility (MHC) locus (MHC restricti ....Unrestricted antigen recognition by T lymphocytes. This project aims to investigate the unrestricted T cell repertoire; the molecular and structural basis of antigen recognition by unrestricted T cells; and the development of unrestricted T cells. T lymphocytes typically are restricted to detecting foreign molecules (antigens) on the cell membrane in association with specialised antigen-presenting molecules encoded within the highly polymorphic major histocompatibility (MHC) locus (MHC restriction). T lymphocytes that can recognise antigens in the absence of MHC or MHC like molecules challenges a major paradigm in the field of immunology. As T cell based therapy underpins treatments for cancer and infection, new mechanisms of T cell activation that are independent of patient genotype should ultimately create opportunities for therapeutic and commercial development, leading to both health and economic benefits.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
Molecular determinants of an allergic response. Some humans develop allergies after exposure to environmental allergens while others do not. At present, the reason for this individual variation is not known. By comparing the processes activated in allergic versus non-allergic individuals, this study will identify critical molecules involved in making individuals susceptible to allergies, which will be used to develop safer and more effective allergy vaccines.
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
Whole-body analysis of human tissue-resident memory T cells. T cells provide critical immune protection against infection and cancer, and dysfunctional T cells cause autoimmune disease. Much of our understanding of T cells comes from studies of mice and how these immune cells work in humans is not fully understood. This project aims to determine how human T cells persist and function using a unique organ donor tissue resource. The expected outcomes are to generate fundamental new knowledge about ....Whole-body analysis of human tissue-resident memory T cells. T cells provide critical immune protection against infection and cancer, and dysfunctional T cells cause autoimmune disease. Much of our understanding of T cells comes from studies of mice and how these immune cells work in humans is not fully understood. This project aims to determine how human T cells persist and function using a unique organ donor tissue resource. The expected outcomes are to generate fundamental new knowledge about the regulation of the human immune response. This knowledge is critical for the development of vaccines and immunotherapies designed to harness T cell immunity.Read moreRead less