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
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
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
Functional Genomics and Host Cell Specificity of Herpesviruses. Herpesviruses cause severe diseases in many species, but research on their large DNA genomes has been difficult due to the need to use animal cell cultures for the generation of virus mutants. The cloning of complete herpesvirus genomes as Bacterial Artificial Chromosomes (BACs) has revolutionized herpesvirus genomics, and it is now possible to examine herpesvirus gene functions in unprecedented detail using elegant new mutation tec ....Functional Genomics and Host Cell Specificity of Herpesviruses. Herpesviruses cause severe diseases in many species, but research on their large DNA genomes has been difficult due to the need to use animal cell cultures for the generation of virus mutants. The cloning of complete herpesvirus genomes as Bacterial Artificial Chromosomes (BACs) has revolutionized herpesvirus genomics, and it is now possible to examine herpesvirus gene functions in unprecedented detail using elegant new mutation techniques. The project, based on two related equine herpesviruses, will identify new targets for antiviral drugs or vaccines. These herpesvirus BAC systems represent frontier science that greatly facilitates the study of links between genome and phenome.Read moreRead less
Maintaining fidelity in viral Ribonucleic acid (RNA) polymerases. This project will provide informed insights into the dynamics of viruses that currently impact a healthy start to life, ageing well and productively, and preventative healthcare. The analysis of viruses that cause gastroenteritis outbreaks will increase our understanding of how these viruses replicate and spread.
The geometry of genome access: lessons from HIV. Access to the cell’s nucleus, and hence its genome, is of deep scientific and commercial significance. It is controlled by a phase-separated diffusion barrier within the nuclear pore complex. Recent evidence, however, has shown that HIV can cross this barrier with its protective capsid intact, despite it being over one thousand times larger than the limit for passive transport. Combining concepts from soft-matter physics with recombinant assays, t ....The geometry of genome access: lessons from HIV. Access to the cell’s nucleus, and hence its genome, is of deep scientific and commercial significance. It is controlled by a phase-separated diffusion barrier within the nuclear pore complex. Recent evidence, however, has shown that HIV can cross this barrier with its protective capsid intact, despite it being over one thousand times larger than the limit for passive transport. Combining concepts from soft-matter physics with recombinant assays, this project aims to uncover the link between the unique geometry of HIV capsids and their ability to subvert the nucleus’ defenses. The expected outcome is a step-change in the understanding of nuclear access control, with downstream benefits to virology, bio-engineering and bio-technology.Read moreRead less
Revealing the determinants of viral emergence and evolution in fish. Viral diseases pose an ongoing threat to Australian aquaculture. The devastating impact of emerging viruses makes it imperative to understand the factors that allow them to evolve and infect new hosts. We will address these key issues by revealing the diversity, abundance and evolution of viruses in fish sampled along the Australian east coast. The data generated will reveal the untapped biodiversity of fish viruses, the freque ....Revealing the determinants of viral emergence and evolution in fish. Viral diseases pose an ongoing threat to Australian aquaculture. The devastating impact of emerging viruses makes it imperative to understand the factors that allow them to evolve and infect new hosts. We will address these key issues by revealing the diversity, abundance and evolution of viruses in fish sampled along the Australian east coast. The data generated will reveal the untapped biodiversity of fish viruses, the frequency which they jump species boundaries and the determinants of this process, and how they are impacted by host ecology, including whether fish viruses follow a latitudinal gradient in diversity. The data generated will transform our understanding of fish viruses and identify those most likely to impact aquaculture.Read moreRead less
The fate of single virus particles during infection. This project applies innovative imaging techniques to elucidate the logistics of cellular function. Establishing a cutting-edge technology platform will spawn discovery and research creativity in fundamental science, as well as applications in biomedical and biotechnology research disciplines. We will foster a highly skilled workforce, an essential asset for maintaining and enhancing Australia's reputation and capability as a leader in researc ....The fate of single virus particles during infection. This project applies innovative imaging techniques to elucidate the logistics of cellular function. Establishing a cutting-edge technology platform will spawn discovery and research creativity in fundamental science, as well as applications in biomedical and biotechnology research disciplines. We will foster a highly skilled workforce, an essential asset for maintaining and enhancing Australia's reputation and capability as a leader in research excellence.Read moreRead less
Mechanisms of chronic infection, immunotolerance and coevolution in avian circovirus infections. This project will generate fundamental new knowledge into the pathogenesis of persistent, chronic viral diseases in a wide range of animal hosts. Furthermore, beak and feather disease virus is listed as a Key Threatening Process under the Endangered Species Protection Act (1992) to at least sixteen endangered Australian bird species. Very little is known about the host-virus interactions that occur d ....Mechanisms of chronic infection, immunotolerance and coevolution in avian circovirus infections. This project will generate fundamental new knowledge into the pathogenesis of persistent, chronic viral diseases in a wide range of animal hosts. Furthermore, beak and feather disease virus is listed as a Key Threatening Process under the Endangered Species Protection Act (1992) to at least sixteen endangered Australian bird species. Very little is known about the host-virus interactions that occur during the early stages of infection or why some birds recover yet others develop full blown disease. This project will provide new knowledge that can be used to counteract its effects on current and future endangered species recovery program.Read moreRead less
Regulation of DNA synthesis and host evasion by Lentivirus Capsids. This project aims to investigate how a type of virus, exemplified by HIV, can synthesise DNA in the cytoplasm of a host cell, without triggering the cell’s innate immunity when DNA is detected outside the nucleus. It expects to advance understanding of the role of the virus’ protein shell in regulating DNA synthesis during infection. The project outcomes should include enhanced capacity for fundamental virus and cell biology re ....Regulation of DNA synthesis and host evasion by Lentivirus Capsids. This project aims to investigate how a type of virus, exemplified by HIV, can synthesise DNA in the cytoplasm of a host cell, without triggering the cell’s innate immunity when DNA is detected outside the nucleus. It expects to advance understanding of the role of the virus’ protein shell in regulating DNA synthesis during infection. The project outcomes should include enhanced capacity for fundamental virus and cell biology research in Australia. The project anticipates contributing to new tools for delivering genes to cells, benefiting therapeutic and biotechnology applications.Read moreRead less