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
A New Platform for Developing a Compound Against Herpes Simplex Virus. This project aims to further explore the research team’s recent fundamental discovery of a protein found naturally in an Australian abalone that inhibits viral entry by blocking three key viral glycoproteins. We would aim to utilise this knowledge towards development of a new class of therapeutics against Herpes simplex viruses (HSV) and their consequent infections. The new therapeutics could overcome the low bioavailability ....A New Platform for Developing a Compound Against Herpes Simplex Virus. This project aims to further explore the research team’s recent fundamental discovery of a protein found naturally in an Australian abalone that inhibits viral entry by blocking three key viral glycoproteins. We would aim to utilise this knowledge towards development of a new class of therapeutics against Herpes simplex viruses (HSV) and their consequent infections. The new therapeutics could overcome the low bioavailability of current drugs and thus significantly shorten the recurrence period. Such new drugs may have broad applicability.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
Biological probes for understanding mammalian cellular transport mechanisms. Cellular components are moved around within cells by molecular motors. This fundamental transport mechanism depends on a network of tracks. Blocks in this cellular transport can result in a number of mammalian diseases, particularly within nerve cells. This project will increase our understanding of the mechanisms of cellular transport and, in particular, how molecular motors engage their cargo. This is essential ground ....Biological probes for understanding mammalian cellular transport mechanisms. Cellular components are moved around within cells by molecular motors. This fundamental transport mechanism depends on a network of tracks. Blocks in this cellular transport can result in a number of mammalian diseases, particularly within nerve cells. This project will increase our understanding of the mechanisms of cellular transport and, in particular, how molecular motors engage their cargo. This is essential groundwork for the development of drugs that target this transport mechanism.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
Molecular approaches to solving current and emerging problems in the epidemiology and diagnosis of Marek's disease in Australia. Marek's disease (MD) is a ubiquitous viral disease of chickens that is currently controlled in meat chickens by blanket vaccination of all chickens. However, as has happened overseas, the efficacy of the HVT vaccine being used in Australia is breaking down resulting in subclinical and clinical losses due to MD. To assist industry deal with this situation we propose to ....Molecular approaches to solving current and emerging problems in the epidemiology and diagnosis of Marek's disease in Australia. Marek's disease (MD) is a ubiquitous viral disease of chickens that is currently controlled in meat chickens by blanket vaccination of all chickens. However, as has happened overseas, the efficacy of the HVT vaccine being used in Australia is breaking down resulting in subclinical and clinical losses due to MD. To assist industry deal with this situation we propose to develop novel molecular methods for the quantification of Marek's disease viruses (MDV) in the host and the environment, to use these methods to design effective early monitoring systems for MD in broilers that predict disease and performance outcomes, and to develop an epidemiological model that will predict the spread and severity of MD as failure of vaccinal protection progresses.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