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
Using viral inhibitors to understand the regualtion of apoptosis. Apoptosis is a form of cell death that is critical for the development and well-being of multicellular organisms. The activity of Bak or Bax, two members of the Bcl-2 family, are essential for apoptosis to proceed, but how the activity of these two proteins is regulated is unclear. Many viruses encode inhibitors of apoptosis and the project will make use of two novel viral inhibitors that specifically target Bak. The project aims ....Using viral inhibitors to understand the regualtion of apoptosis. Apoptosis is a form of cell death that is critical for the development and well-being of multicellular organisms. The activity of Bak or Bax, two members of the Bcl-2 family, are essential for apoptosis to proceed, but how the activity of these two proteins is regulated is unclear. Many viruses encode inhibitors of apoptosis and the project will make use of two novel viral inhibitors that specifically target Bak. The project aims to determine how the Bak inhibitors function and to provide valuable insights into the normal mechanisms regulating Bak activity.Read moreRead less
Role of plant host factors in the replication and pathogenesis of Tomato leaf curl virus (TLCV). Geminivirus infection is an emerging problem in the Australian tomato growing industry which is currently worth ca.A$200m annually. Knowledge gained from this research will have direct benefit in safeguarding this industry by providing an insight into geminivirus replication and identifying molecular targets for virus control. More generally, the technology developed through this study will contribu ....Role of plant host factors in the replication and pathogenesis of Tomato leaf curl virus (TLCV). Geminivirus infection is an emerging problem in the Australian tomato growing industry which is currently worth ca.A$200m annually. Knowledge gained from this research will have direct benefit in safeguarding this industry by providing an insight into geminivirus replication and identifying molecular targets for virus control. More generally, the technology developed through this study will contribute to our basic understanding of virus replication in plants with a view to controlling virus diseases by direct molecular intervention with specifically engineered tools. We foresee potential industrial applications. Read moreRead less
Seeking causes of unexplained respiratory illness in children by identifying new respiratory viruses. Many respiratory illnesses including the common cold, ear infections, asthma attacks, the flu and pneumonia have no known cause even after all specimen testing is complete. This project will use 'virus hunting' experience to find and sequence as-yet-undiscovered viruses from such specimens so that they can be studied in more detail.
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.
Kingdom switching microbial pathogens: the bioinformatics of mutation in the genomes of viruses and bacteria affecting crops, livestock and people. Some organisms that cause infectious diseases have moved between plants and vertebrates, either recently or repeatedly over evolutionary time. Switching between plants and vertebrates strongly influences the way these microbes mutate and evolve. We will search the genomic sequence databases for information about how the choice of host influences muta ....Kingdom switching microbial pathogens: the bioinformatics of mutation in the genomes of viruses and bacteria affecting crops, livestock and people. Some organisms that cause infectious diseases have moved between plants and vertebrates, either recently or repeatedly over evolutionary time. Switching between plants and vertebrates strongly influences the way these microbes mutate and evolve. We will search the genomic sequence databases for information about how the choice of host influences mutations in viral and bacterial genomes and model the evolutionary processes involved. This project will advance our understanding of the fine structure of microbial genomes and the importance of selection pressures on genes. It will lead to better disease management strategies for humans, and for domestic crops and livestock.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