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
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
The role of immuno-exosomes in innate immunity. This project aims to determine the role of exosomes (EV) in innate immunity. Exosomes are extracellular vesicles secreted by mammalian cells that have an important biological function in intercellular communication by transferring biologically active proteins, lipids, and RNAs to neighbouring or distant cells. Following exposure to a foreign organism, cells dynamically change the protein composition of the EV they secrete. While this data supports ....The role of immuno-exosomes in innate immunity. This project aims to determine the role of exosomes (EV) in innate immunity. Exosomes are extracellular vesicles secreted by mammalian cells that have an important biological function in intercellular communication by transferring biologically active proteins, lipids, and RNAs to neighbouring or distant cells. Following exposure to a foreign organism, cells dynamically change the protein composition of the EV they secrete. While this data supports a role for EV as key players in innate immunity, a full understanding of the biological relevance of these vesicles and how they serve as a cellular defence mechanism is lacking. This project will provide significant benefits such as addressing key questions in EV biology and providing new fundamental insights into a novel and poorly understood component of the innate immune response.Read moreRead less
Unravelling small RNA regulatory networks to target and control bacteria. Small RNA (sRNA) molecules are critical regulators of bacterial gene expression. These molecules control important phenotypes in the Gram-negative veterinary pathogen Pasteurella multocida. This project aims to identify the range of P. multocida sRNAs and to show how expression of these molecules changes under various growth conditions. Specifically, this project endeavours: to identify the mRNA targets of the sRNAs; to id ....Unravelling small RNA regulatory networks to target and control bacteria. Small RNA (sRNA) molecules are critical regulators of bacterial gene expression. These molecules control important phenotypes in the Gram-negative veterinary pathogen Pasteurella multocida. This project aims to identify the range of P. multocida sRNAs and to show how expression of these molecules changes under various growth conditions. Specifically, this project endeavours: to identify the mRNA targets of the sRNAs; to identify the mechanisms of sRNA-mRNA interaction; to build systems-biology models that describe the sRNA regulatory circuits; to design inhibitors capable of disrupting critical sRNA-mRNA interactions; and to use the new inhibitors to modulate specific phenotypes. The ability to precisely manipulate sRNA regulatory circuits could allow fine control of bacterial phenotypes and could be widely applicable.Read moreRead less
What is killing the honeybees? The role of RNA viruses. This project aims to determine if the Varroa mite, the most important parasite of honeybees, selects for virulent strains of RNA viruses. Before Varroa’s inevitable arrival in Australia, this project will disentangle the effect of Varroa and the bees’ immune system on the evolution of virulence of bee viruses. Australia’s honeybees are Varroa-naïve and don’t carry virulent viruses. There is a known association between Varroa and colonies dy ....What is killing the honeybees? The role of RNA viruses. This project aims to determine if the Varroa mite, the most important parasite of honeybees, selects for virulent strains of RNA viruses. Before Varroa’s inevitable arrival in Australia, this project will disentangle the effect of Varroa and the bees’ immune system on the evolution of virulence of bee viruses. Australia’s honeybees are Varroa-naïve and don’t carry virulent viruses. There is a known association between Varroa and colonies dying from viruses; however, it is not known what is cause and effect. This project will clarify Varroa’s exact role in the evolution of virulence in RNA viruses. The intended outcome is increased knowledge allowing the design of an effective treatment to prevent the death of honeybee colonies.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE190101053
Funder
Australian Research Council
Funding Amount
$421,656.00
Summary
Archaeal vesicles: new insights into viral evolution and DNA transfer. This project aims to determine the basis for plasmid and membrane vesicle generation and DNA transfer at the cellular and molecular level. Recent discovery of plasmid vesicles, which transfer plasmid DNA between host cells using viral capsid-like membrane vesicles, suggests they may be an evolutionary precursor for virus particles. The expected project outcomes include the first substantive characterisation of membrane vesicl ....Archaeal vesicles: new insights into viral evolution and DNA transfer. This project aims to determine the basis for plasmid and membrane vesicle generation and DNA transfer at the cellular and molecular level. Recent discovery of plasmid vesicles, which transfer plasmid DNA between host cells using viral capsid-like membrane vesicles, suggests they may be an evolutionary precursor for virus particles. The expected project outcomes include the first substantive characterisation of membrane vesicles in the phylum Euryarchaeota, how plasmid vesicles are generated and transmitted, and new insights into how viruses may evolve. This may lead to new avenues for preventing viral transmission and supporting development of new and improved applications biotechnology and the safe delivery of vaccines or genes in animals and humans.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
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.
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
Evolutionary history and impact of adeno-associated viruses in Australia. Recently accrued evidence identifies Australia as an ideal closed-model system in which to elucidate the evolutionary history of a group of non-pathogenic viruses, known as adeno-associated viruses (AAVs). This project aims to trace back the evolutionary history of AAVs for tens of millions of years via molecular fossil imprints left behind by ancient viral invasions of Australian marsupial genomes. Concurrently, the poten ....Evolutionary history and impact of adeno-associated viruses in Australia. Recently accrued evidence identifies Australia as an ideal closed-model system in which to elucidate the evolutionary history of a group of non-pathogenic viruses, known as adeno-associated viruses (AAVs). This project aims to trace back the evolutionary history of AAVs for tens of millions of years via molecular fossil imprints left behind by ancient viral invasions of Australian marsupial genomes. Concurrently, the potential impact that these viral invasions had on the evolutionary development of their ancestral hosts will be investigated. This could facilitate previously unattainable insights into both AAV and marsupial evolution, with broader implications relevant to the advancement of the fields of virology and mammalian evolution.Read moreRead less