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
Microcrystallography of spheroids: crystalline armours of insect viruses. The proposed project will provide fundamental insights into the organisation of ultra-stable armours protecting insect viruses. This will open novel avenues for the development of highly efficient and specific bioinsectides as well as innovative tools such as natural microparticles for improved vaccines.
The techniques used in this project are at the frontier of imaging techniques and will establish a national expertise i ....Microcrystallography of spheroids: crystalline armours of insect viruses. The proposed project will provide fundamental insights into the organisation of ultra-stable armours protecting insect viruses. This will open novel avenues for the development of highly efficient and specific bioinsectides as well as innovative tools such as natural microparticles for improved vaccines.
The techniques used in this project are at the frontier of imaging techniques and will establish a national expertise in X-ray micro-crystallography. This will contribute to the optimal use of the $8-million microfocus beamline of the newly built Australian Synchrotron enabling breakthroughs such as the structures of membrane receptors for hormone and neurotransmitter with major implications for drug development.Read moreRead less
Blocking immune responses: a critical factor in herpesvirus virulence? The horse and poultry industries are two large, primarily rural based livestock production industries that are major contributors to the national economy. The research proposed in this project will improve our understanding of the pathogenesis of two important viral pathogens that are each a significant cost to their respective industry, and thus will ultimately reduce the cost of these two viruses to industry. In addition, ....Blocking immune responses: a critical factor in herpesvirus virulence? The horse and poultry industries are two large, primarily rural based livestock production industries that are major contributors to the national economy. The research proposed in this project will improve our understanding of the pathogenesis of two important viral pathogens that are each a significant cost to their respective industry, and thus will ultimately reduce the cost of these two viruses to industry. In addition, the technology developed during this project would have a global market and may be transferable to other viral pathogens of other domestic species.Read moreRead less
Nucleolus targeting by negative strand RNA viruses. Negative strand viruses (NSVs) include diverse animal pathogens that represent significant threats to Australian livestock industries and access to export markets. The project aims to investigate the interface formed by NSVs with cellular nucleoli in order to determine roles in viral manipulation of cell biology during infection. This project hopes to address a major gap in knowledge in virology regarding the fundamental biology of NSVs, and is ....Nucleolus targeting by negative strand RNA viruses. Negative strand viruses (NSVs) include diverse animal pathogens that represent significant threats to Australian livestock industries and access to export markets. The project aims to investigate the interface formed by NSVs with cellular nucleoli in order to determine roles in viral manipulation of cell biology during infection. This project hopes to address a major gap in knowledge in virology regarding the fundamental biology of NSVs, and is expected to redefine our understanding of the virus-host interactions formed by these important pathogens. By determining the mechanisms of NSV-nucleolus interaction, the project plans to also provide important information for the development of new vaccines/therapeutics for livestock to combat NSVs that target nucleoli.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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Uncovering mechanisms of protein multifunctionality. This project aims to use viral proteins to uncover fundamental mechanisms underlying protein multifunctionality, a central but poorly understood aspect of biology. This project expects to use multidisciplinary approaches to define novel and unexpected mechanisms by which single protein sequences can generate proteins with profoundly different structures and functions. Expected outcomes include a major shift in the understanding of protein fun ....Uncovering mechanisms of protein multifunctionality. This project aims to use viral proteins to uncover fundamental mechanisms underlying protein multifunctionality, a central but poorly understood aspect of biology. This project expects to use multidisciplinary approaches to define novel and unexpected mechanisms by which single protein sequences can generate proteins with profoundly different structures and functions. Expected outcomes include a major shift in the understanding of protein function in life, with most immediate impact in virology. This should provide significant benefits in identifying new strategies for treating viral infections, but also enhance developing multidisciplinary approaches to solve complex biological problems.Read moreRead less
The viral fusosome: a modular machinery for cargo delivery to target cells. The delivery of proteins, RNA and DNA into cells is a critical process in normal cellular biology, virus infection and biotechnology applications such as gene editing. Enveloped viruses achieve this maneuver with exquisite efficiency and specificity using a complex machinery mediating their fusion with cellular membranes for stealth genome delivery. Remarkably, all characterised viral fusion proteins belong to only 3 cla ....The viral fusosome: a modular machinery for cargo delivery to target cells. The delivery of proteins, RNA and DNA into cells is a critical process in normal cellular biology, virus infection and biotechnology applications such as gene editing. Enveloped viruses achieve this maneuver with exquisite efficiency and specificity using a complex machinery mediating their fusion with cellular membranes for stealth genome delivery. Remarkably, all characterised viral fusion proteins belong to only 3 classes defined >16 years ago and sharing surprisingly conserved mechanisms. We identified a novel class of fusion proteins with unique architecture in ubiquitous insect viruses. The Project will elucidate the structural and functional hallmarks of this fusion machinery providing a platform for its engineering.Read moreRead less
Defining the antiviral effects of Wolbachia in Aedes aegypti mosquitoes. Mosquitoes that carry a bacterium called Wolbachia do not transmit human pathogenic viruses. These mosquitoes are being developed as a biocontrol tool to prevent mosquito-borne diseases. This project aims to define the molecular basis for virus inhibition by Wolbachia. Using unique biological tools including mosquitoes carrying different strains of Wolbachia that do or do not inhibit dengue virus, the project will define ho ....Defining the antiviral effects of Wolbachia in Aedes aegypti mosquitoes. Mosquitoes that carry a bacterium called Wolbachia do not transmit human pathogenic viruses. These mosquitoes are being developed as a biocontrol tool to prevent mosquito-borne diseases. This project aims to define the molecular basis for virus inhibition by Wolbachia. Using unique biological tools including mosquitoes carrying different strains of Wolbachia that do or do not inhibit dengue virus, the project will define how Wolbachia modifies its host to create an antiviral state. The findings will provide insight into how viral pathogens can be suppressed in insect hosts. This may guide future viral disease intervention strategies for diverse areas afflicted by insect-borne viral disease, including human health and agriculture.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