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
Do insect-specific flaviviruses regulate the transmission of mosquito-borne diseases in Australia? Mosquito-borne viral diseases such as dengue occur in Australia. The research team recently discovered related viruses in mosquitoes from Darwin that do not infect humans, but may inhibit the spread of viral diseases by mosquitoes. This project will investigate the life cycles of these new viruses to understand how they affect the spread of viral diseases by mosquitoes.
Revealing the evolutionary and ecological dynamics of avian influenza virus. This project aims to understand how avian influenza virus (AIV) emerges, evolves and spreads in wild birds. AIV has the potential to devastate the poultry industry and cause human pandemics, but the factors that shape the genetic diversity of AIV in its wild bird reservoir are poorly understood. The project plans to combine genomic, ecological and phylogenetic approaches to reveal key aspects of AIV evolution, as well a ....Revealing the evolutionary and ecological dynamics of avian influenza virus. This project aims to understand how avian influenza virus (AIV) emerges, evolves and spreads in wild birds. AIV has the potential to devastate the poultry industry and cause human pandemics, but the factors that shape the genetic diversity of AIV in its wild bird reservoir are poorly understood. The project plans to combine genomic, ecological and phylogenetic approaches to reveal key aspects of AIV evolution, as well as the risk for future viral emergence. Using sampling sites in Australia and Antarctica, it plans to investigate AIV diversity, the evolutionary dynamics of AIV in wild birds and poultry, and the role played by environmental transmission in AIV ecology.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
From shape to function: how structured RNA defines insect flaviviruses. The goal of this project is to obtain an understanding of how insect-specific flaviviruses (ISFs) utilise viral noncoding RNAs to enable their replication in mosquitoes. These viruses only replicate in mosquitoes, and not in humans or animals. They can be employed as the biocontrol agents for mosquito-borne diseases as they make mosquitoes incapable of disease transmission. However, it is currently unknown how exactly insect ....From shape to function: how structured RNA defines insect flaviviruses. The goal of this project is to obtain an understanding of how insect-specific flaviviruses (ISFs) utilise viral noncoding RNAs to enable their replication in mosquitoes. These viruses only replicate in mosquitoes, and not in humans or animals. They can be employed as the biocontrol agents for mosquito-borne diseases as they make mosquitoes incapable of disease transmission. However, it is currently unknown how exactly insect-specific flaviviruses affect mosquitoes and this information is vital for informed design of ISF-based interventions. The project will generate new knowledge on functions of noncoding RNAs in ISFs that are hypothesised to have immunomodulatory role in mosquitoes. It will also train students and ECRs.Read moreRead less
The effect of age on regulatory T cell control of the innate and adaptive antiviral immune responses. Viral pathogens are a lead cause of infant mortality in the world. This project will define how T regulatory cells limit protective antiviral immune responses in the young. This information is critical for the development of potent antiviral vaccines that are effective from the newborn period without inducing autoimmunity. It will also provide novel insight into the way T regulatory cells can b ....The effect of age on regulatory T cell control of the innate and adaptive antiviral immune responses. Viral pathogens are a lead cause of infant mortality in the world. This project will define how T regulatory cells limit protective antiviral immune responses in the young. This information is critical for the development of potent antiviral vaccines that are effective from the newborn period without inducing autoimmunity. It will also provide novel insight into the way T regulatory cells can be manipulated both to dampen immunity, which can be used to develop strategies to reduce immune mediated disease and limit transplant rejection. Read moreRead less
Noncanonical epitope recognition by CD8+ T lymphocytes. This proposed research program will provide significant fundamental insight in the areas of immunology and vaccine design. Vaccines for many diseases remain elusive, and this project aims to improve our understanding of the precise regions within pathogens that are the targets for the killer T cells of the immune system. These regions, called epitopes, are likely to be key ingredients in many future vaccines. Although immunologists have gat ....Noncanonical epitope recognition by CD8+ T lymphocytes. This proposed research program will provide significant fundamental insight in the areas of immunology and vaccine design. Vaccines for many diseases remain elusive, and this project aims to improve our understanding of the precise regions within pathogens that are the targets for the killer T cells of the immune system. These regions, called epitopes, are likely to be key ingredients in many future vaccines. Although immunologists have gathered much information about such epitopes, recent studies have shown that some unexpected regions of pathogens are targets for killer T cells. This project will break new ground by utilising unbiased procedures to assess the relative contribution of these noncanonical epitopes to immunity.Read moreRead less
Regulation of MHC-I and ICAM-1 by flavivirus, West Nile. This project investigates the intracellular signalling pathway responsible for the expression of genes which are critical to our immune response. We have demonstrated in a mouse model that high levels of expression of two of these genes in flavivirus encephalitis are associated with a survival advantage. We would expect this project to provide basic new information about the mechanisms of expression of these genes as well as information ab ....Regulation of MHC-I and ICAM-1 by flavivirus, West Nile. This project investigates the intracellular signalling pathway responsible for the expression of genes which are critical to our immune response. We have demonstrated in a mouse model that high levels of expression of two of these genes in flavivirus encephalitis are associated with a survival advantage. We would expect this project to provide basic new information about the mechanisms of expression of these genes as well as information about the interaction of this family of viruses, flavivirus with the host.Read moreRead less