Discovery Early Career Researcher Award - Grant ID: DE120100691
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Argonaute proteins and the mammalian antiviral response. Awarded the Nobel Prize for Medicine in 2006, RNA interference (RNAi) is a natural process that plants use to attack viruses. Humans possess all of the tools for RNAi, but whether it is used for antiviral defense is unknown. This project aims to uncover this immune process which will open new avenues to treat virus infections, from influenza to HIV.
The role of the innate immune response in the asymptomatic nature of viral infections in bats. Bats are natural reservoirs to a variety of viruses, including many that are lethal in humans and other mammals. This project will generate fundamental information on the mechanisms involved in the asymptomatic nature of viral infections in bats and contribute towards the development of new antiviral strategies for other susceptible species.
The role of immuno-exosomes in innate immunity. This project aims to determine the role of exosomes (EV) in innate immunity. Exosomes are extracellular vesicles secreted by mammalian cells that have an important biological function in intercellular communication by transferring biologically active proteins, lipids, and RNAs to neighbouring or distant cells. Following exposure to a foreign organism, cells dynamically change the protein composition of the EV they secrete. While this data supports ....The role of immuno-exosomes in innate immunity. This project aims to determine the role of exosomes (EV) in innate immunity. Exosomes are extracellular vesicles secreted by mammalian cells that have an important biological function in intercellular communication by transferring biologically active proteins, lipids, and RNAs to neighbouring or distant cells. Following exposure to a foreign organism, cells dynamically change the protein composition of the EV they secrete. While this data supports a role for EV as key players in innate immunity, a full understanding of the biological relevance of these vesicles and how they serve as a cellular defence mechanism is lacking. This project will provide significant benefits such as addressing key questions in EV biology and providing new fundamental insights into a novel and poorly understood component of the innate immune response.Read moreRead less
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.
Virus and host genes and the outcome of infection. Viruses cause infection of all animals including people and the outcome of infection is highly variable. This project aims to use genetics to explain why some animals are more susceptible to particular virus infections and some strains of virus cause more severe diseases. The project will also explore whether all cells are similarly susceptible to killing by viruses.
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