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
Defining novel immune checkpoints controlled by stromal cells. This project seeks to use innovative approaches to elucidate the mechanisms that define the earliest steps required to generate immune responses. The proposal builds on discoveries, including novel preliminary data, from a team with world-leading expertise in immunology, virology and stromal cell biology. The expected findings will provide fundamental insights into novel cellular and molecular interactions between stromal tissue comp ....Defining novel immune checkpoints controlled by stromal cells. This project seeks to use innovative approaches to elucidate the mechanisms that define the earliest steps required to generate immune responses. The proposal builds on discoveries, including novel preliminary data, from a team with world-leading expertise in immunology, virology and stromal cell biology. The expected findings will provide fundamental insights into novel cellular and molecular interactions between stromal tissue components and immune cells that initiate and regulate immune responses. Expected benefits include fundamental advances in knowledge, as well as insights that will ultimately benefit biotechnology and therapeutic applications, and in this way support research priorities linked to advanced manufacturing and health.
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Biotechnology and epidemiology to control nodavirus in barramundi aquaculture. Production of farmed barramundi has increased more than 1200% in the NT since 2001 but is threatened by nodavirus infection. Three industry partners, Darwin Aquaculture Centre, Marine Harvest and Berrimah Veterinary Laboratory will collaborate with The University of Sydney to:
1. control nodavirus infection
2. develop new technologies to detect nodavirus using immunoassay and surface enhanced laser desorption ionis ....Biotechnology and epidemiology to control nodavirus in barramundi aquaculture. Production of farmed barramundi has increased more than 1200% in the NT since 2001 but is threatened by nodavirus infection. Three industry partners, Darwin Aquaculture Centre, Marine Harvest and Berrimah Veterinary Laboratory will collaborate with The University of Sydney to:
1. control nodavirus infection
2. develop new technologies to detect nodavirus using immunoassay and surface enhanced laser desorption ionisation mass spectroscopy (SELDI)
3. develop an integrated disease control strategy based on epidemiological survey data, and ensure that it is practical and able to be widely adopted
By this means growth targets for barramundi aquaculture in northern Australia will be achieved.
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Dissecting the Parameters for the Generation of Cytotoxic T Lymphocyte Immunity. This project aims to identify mechanisms by which antigen-presenting cells, such as dendritic cells, prime CD8+ T cells to generate effector and memory populations at the molecular level. The specific intention is to identify reagents capable of licensing dendritic cells, and examine the down-stream gene products/pathways generated by these signals using microarray analyses. Such knowledge will provide new insight i ....Dissecting the Parameters for the Generation of Cytotoxic T Lymphocyte Immunity. This project aims to identify mechanisms by which antigen-presenting cells, such as dendritic cells, prime CD8+ T cells to generate effector and memory populations at the molecular level. The specific intention is to identify reagents capable of licensing dendritic cells, and examine the down-stream gene products/pathways generated by these signals using microarray analyses. Such knowledge will provide new insight into CTL generation by providing greater understanding of how multicellular systems function both at the cellular and molecular level.Read moreRead less
Imaging of immune responses to pathogens in vivo. This proposal represents an excellent opportunity for Australian science to participate in state-of-the-art research into the immune system and to be internationally competitive with the best researchers in the field. By combining advanced microscopy techniques with well developed biological models used by researchers at the University of Melbourne, this project will greatly improve our understanding of the dynamic interactions that occur betwee ....Imaging of immune responses to pathogens in vivo. This proposal represents an excellent opportunity for Australian science to participate in state-of-the-art research into the immune system and to be internationally competitive with the best researchers in the field. By combining advanced microscopy techniques with well developed biological models used by researchers at the University of Melbourne, this project will greatly improve our understanding of the dynamic interactions that occur between cells of the immune system during infectious diseases. The insight provided by this project will facilitate the design of better vaccines for protection against diseases, including influenza.Read moreRead less
Equine rhinitis A virus; molecular pathogenesis and methods for control. The horse industry in Australia is primarily based in rural locations and is a major contributor to the national economy both in terms of direct economic contribution to gross domestic product and as a major employer of people in regional Australia. The research proposed in this project will improve our understanding of the pathogenesis of a virus that causes respiratory disease in horses that is related to the virus that c ....Equine rhinitis A virus; molecular pathogenesis and methods for control. The horse industry in Australia is primarily based in rural locations and is a major contributor to the national economy both in terms of direct economic contribution to gross domestic product and as a major employer of people in regional Australia. The research proposed in this project will improve our understanding of the pathogenesis of a virus that causes respiratory disease in horses that is related to the virus that causes foot and mouth disease in ruminants and swine. The technology developed during this project would have a global market.Read moreRead less
Studies on peripheral T cell memory. Success in vaccination depends on the ability of the immune system to remember prior encounter with an infectious agent. This immune memory appears to work well for certain infections but not others, essentially meaning that for these diseases, effective vaccines remain unavailable. This application describes experiments based on a new leukocyte or white blood cell population that has been overlooked in studies of immune memory. The work involves identifyin ....Studies on peripheral T cell memory. Success in vaccination depends on the ability of the immune system to remember prior encounter with an infectious agent. This immune memory appears to work well for certain infections but not others, essentially meaning that for these diseases, effective vaccines remain unavailable. This application describes experiments based on a new leukocyte or white blood cell population that has been overlooked in studies of immune memory. The work involves identifying how they are formed and how they behave within the body. This work will therefore contribute to the development and production of new-generation vaccines to these so far uncontrollable infectious diseases.Read moreRead less
Mechanisms of infertility induced in mice by vaccination with murine zona pellucida 3. This research investigates the means by which a novel immunocontraceptive vaccine induces an infertile state in female mice. The vaccine stimulates an autoimmune condition which resembles certain naturally occurring ovarian diseases. By investigating how ovarian cellular interactions are maintained in normal ovaries and disrupted by the immunocontraceptive vaccine, we will learn a great deal about ovarian fu ....Mechanisms of infertility induced in mice by vaccination with murine zona pellucida 3. This research investigates the means by which a novel immunocontraceptive vaccine induces an infertile state in female mice. The vaccine stimulates an autoimmune condition which resembles certain naturally occurring ovarian diseases. By investigating how ovarian cellular interactions are maintained in normal ovaries and disrupted by the immunocontraceptive vaccine, we will learn a great deal about ovarian function in health and disease. Ultimately this information will be applied to improving the reproductive health of women.
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Development of purified antibodies that kill virus infected cells. This proposal will develop panels of purified and monoclonal antibodies that kill virus infected cells. These antibodies may show efficacy in preventing HIV infection. This is new technology that could subsequently be harnessed to protect or limit the devastating effects of chronic viruses such as HIV.
Retroviral invasion of the koala genome: prevalence, transmission and role in immunosuppressive disease. Koalas are a national symbol yet many of their populations are in decline as a result of habitat loss and disease. Lymphoid cancers and opportunistic infections are significant diseases in both captive and wild koala populations. We previously demonstrated that the recently identified koala retrovirus is associated with lymphoid cancer in koalas. This project will determine the distribution o ....Retroviral invasion of the koala genome: prevalence, transmission and role in immunosuppressive disease. Koalas are a national symbol yet many of their populations are in decline as a result of habitat loss and disease. Lymphoid cancers and opportunistic infections are significant diseases in both captive and wild koala populations. We previously demonstrated that the recently identified koala retrovirus is associated with lymphoid cancer in koalas. This project will determine the distribution of the virus in Australia, the mechanism of its spread and its effect on the immune function of koalas. This research will provide a foundation for better management of captive koalas and for conservation of wild koalas.Read moreRead less