Noncoding RNAs of insect-specific flaviviruses: biogenesis and functions. This project aims to investigate noncoding RNAs (sfRNAs) of insect-specific flaviruses (ISFs). These RNAs are produced from viral RNA by host ribonuclease and play important role in pathogenesis and transmission of vertebrate-infecting flaviviruses (VIFs). The team has shown that ISFs also produce sfRNAs although likely employing a different mechanism. The project expects to generate new knowledge on ISF sfRNA biogenesis a ....Noncoding RNAs of insect-specific flaviviruses: biogenesis and functions. This project aims to investigate noncoding RNAs (sfRNAs) of insect-specific flaviruses (ISFs). These RNAs are produced from viral RNA by host ribonuclease and play important role in pathogenesis and transmission of vertebrate-infecting flaviviruses (VIFs). The team has shown that ISFs also produce sfRNAs although likely employing a different mechanism. The project expects to generate new knowledge on ISF sfRNA biogenesis and functions using combination of modern structural, biochemical, and innovative molecular virology methods. The outcome will be a clearer understanding of processes governing flavivirus host restriction and evolution. This will improve understanding of virus-host interactions and train students in cutting edge techniques.Read moreRead less
Functional identification of vaccine targets in pathogenic mycoplasmas. Mycoplasmas are important bacterial pathogens in domestic animals that are incompletely controlled by current vaccines. As a result current control measures for the diseases they cause rely on ongoing treatment with antibiotics. This project will aim to use functional genomics and metabolomics to determine the function of specific surface proteins of a model mycoplasma to identify targets for novel approaches to vaccines aga ....Functional identification of vaccine targets in pathogenic mycoplasmas. Mycoplasmas are important bacterial pathogens in domestic animals that are incompletely controlled by current vaccines. As a result current control measures for the diseases they cause rely on ongoing treatment with antibiotics. This project will aim to use functional genomics and metabolomics to determine the function of specific surface proteins of a model mycoplasma to identify targets for novel approaches to vaccines against these pathogens, and to then assess the potential for inclusion of these proteins in vaccines. Ultimately this will lead to improved vaccines against these important pathogens, improving agricultural productivity and reducing the use of antibiotics in intensively raised livestock.Read moreRead less
The cellular basis of sex-specific responses to virus infection. This project aims to explore how the sex of cells impacts virus infections in culture. To date, the sex of cells in culture has been overlooked as an important source of biological variability, but may be found to affect basic science through to anti-viral drug discovery. Using a model in which a virus can be adapted to grow better in cells of a single sex, this project expects to generate new knowledge about how sex differences im ....The cellular basis of sex-specific responses to virus infection. This project aims to explore how the sex of cells impacts virus infections in culture. To date, the sex of cells in culture has been overlooked as an important source of biological variability, but may be found to affect basic science through to anti-viral drug discovery. Using a model in which a virus can be adapted to grow better in cells of a single sex, this project expects to generate new knowledge about how sex differences impact virus-host interactions. This project expects to provide new insights into sex-based differences in how cells detect and respond to virus infection, and the extent to which the sex of cells impacts viruses in general.Read moreRead less
Harnessing innate immunity to mitigate bovine respiratory disease. Bovine Respiratory Disease (BRD) is the most significant health problem faced by the beef industry worldwide, causing economic losses of up to $40 million annually in Australia alone. This Project aims to assess an immunostimulant for its ability to induce resistance to infection with bovine respiratory viruses associated with BRD. The Project is expected to generate fundamental new knowledge in veterinary virology. Expected outc ....Harnessing innate immunity to mitigate bovine respiratory disease. Bovine Respiratory Disease (BRD) is the most significant health problem faced by the beef industry worldwide, causing economic losses of up to $40 million annually in Australia alone. This Project aims to assess an immunostimulant for its ability to induce resistance to infection with bovine respiratory viruses associated with BRD. The Project is expected to generate fundamental new knowledge in veterinary virology. Expected outcomes include scholarly publications. The Project will provide significant benefits, such as advances to fundamental knowledge, training of higher research degree students and proof-of-concept data to promote collaborations with commercial partners to develop novel treatment strategies to limit BRD.Read moreRead less
Hyperactive endogenous retroviruses and their impact on the koala genome. Koala populations are in steep decline with the ubiquitous koala retrovirus (KoRV) strongly linked with disease. KoRV and other less studied endogenous retrovirus (ERVs) are extremely active within the genome of koalas to a level never observed in any other vertebrate genome. This study will map ERV integration sites within koalas from across their geographic range country and use long-read genomics approaches to understan ....Hyperactive endogenous retroviruses and their impact on the koala genome. Koala populations are in steep decline with the ubiquitous koala retrovirus (KoRV) strongly linked with disease. KoRV and other less studied endogenous retrovirus (ERVs) are extremely active within the genome of koalas to a level never observed in any other vertebrate genome. This study will map ERV integration sites within koalas from across their geographic range country and use long-read genomics approaches to understand the link between KoRV and other ERVs, the impact on koala caused by dramatic genomic rewiring, and the mechanisms of genomic immunity which supress ERV activity and mitigate disease. Findings will provide insights into the ongoing arms race between virus and host and inform conservation of an iconic species.Read moreRead less
Molecular approaches to limit herpesvirus recombination. This project aims to generate safer attenuated herpesvirus vaccines for use in veterinary medicine by genetically manipulating the herpesvirus genome to reduce virus recombination. Recombination is recognised as a safety concern for a range of attenuated herpesvirus vaccines. This project is expected to generate viruses that have an impaired capacity to recombine with other viruses. These viruses will then be tested as candidate vaccines f ....Molecular approaches to limit herpesvirus recombination. This project aims to generate safer attenuated herpesvirus vaccines for use in veterinary medicine by genetically manipulating the herpesvirus genome to reduce virus recombination. Recombination is recognised as a safety concern for a range of attenuated herpesvirus vaccines. This project is expected to generate viruses that have an impaired capacity to recombine with other viruses. These viruses will then be tested as candidate vaccines for use in veterinary medicine. This offers a new approach to developing safer veterinary vaccines that will benefit our important animal industries.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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Imperfect vaccination drives herpesvirus evolution through recombination. Vaccines are used to help control disease caused by herpesviruses in animals, but some vaccination programs may drive the evolution and spread of herpesviruses with increased fitness (transmissibility, replication and virulence) through recombination. This project aims to study an important avian herpesvirus (infectious laryngotracheitis virus) in the natural host (poultry) to gain fundamental knowledge of how vaccination ....Imperfect vaccination drives herpesvirus evolution through recombination. Vaccines are used to help control disease caused by herpesviruses in animals, but some vaccination programs may drive the evolution and spread of herpesviruses with increased fitness (transmissibility, replication and virulence) through recombination. This project aims to study an important avian herpesvirus (infectious laryngotracheitis virus) in the natural host (poultry) to gain fundamental knowledge of how vaccination programs influence the emergence of diverse recombinant viruses, and identify which types of vaccination programs are best at preventing the emergence of fitter and more virulent viruses. The results are expected to inform vaccination practices to allow more effective control of these viruses in poultry and other animals.Read moreRead less
Quantitative Metagenomics. This project aims to revolutionize our view of the microbial world once more by transforming microbiome studies from relative counts of organisms to actual numbers of microbes. This project expects to impact all the microbiome studies that are being performed worldwide by unveiling the actual numbers of microbes. Expected outcomes of this project include new techniques to enumerate the number of bacteria in different environments and new approaches to measure gene expr ....Quantitative Metagenomics. This project aims to revolutionize our view of the microbial world once more by transforming microbiome studies from relative counts of organisms to actual numbers of microbes. This project expects to impact all the microbiome studies that are being performed worldwide by unveiling the actual numbers of microbes. Expected outcomes of this project include new techniques to enumerate the number of bacteria in different environments and new approaches to measure gene expression within individual bacteria in any environment that will be demonstrated with complex microbial communities. This should provide significant benefits because microbes affect every aspect of our lives and those effects are driven by how many microbes are present.Read moreRead less
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