Discovery Early Career Researcher Award - Grant ID: DE230101284
Funder
Australian Research Council
Funding Amount
$397,003.00
Summary
Insect-specific virus host restriction. Mosquito-borne viruses are a topic of intense research due to their complex biology, ecology and evolution, and their potential to produce unpredictable outbreaks of disease in both humans and animals. Insect-specific viruses (ISVs) are viruses that replicate solely in mosquito cell and are unable to infect vertebrate tissues. This project aims to assess the biodiversity of ISVs in the Australian mosquito population and identify key factors behind their re ....Insect-specific virus host restriction. Mosquito-borne viruses are a topic of intense research due to their complex biology, ecology and evolution, and their potential to produce unpredictable outbreaks of disease in both humans and animals. Insect-specific viruses (ISVs) are viruses that replicate solely in mosquito cell and are unable to infect vertebrate tissues. This project aims to assess the biodiversity of ISVs in the Australian mosquito population and identify key factors behind their restriction in vertebrates. The objectives of the studies proposed will answer clearly defined important biological questions about ISVs, while also delivering technological advances, novel reagents and potential commercial outcomes for the control and prevention of arboviral disease. Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE220101221
Funder
Australian Research Council
Funding Amount
$453,614.00
Summary
Revealing bat antibody recognition mechanism against bat-borne viruses. Bats act as asymptomic reservoir hosts for numerous zoonotic viruses that are lethal in humans, indicating that the bat immune system can control these viruses. However, little is known about bat immunity including how bat antibodies recognise bat-borne viruses. This project aims to study bat anti-viral antibodies by utilising innovative protein engineering, cutting-edge cryo-EM technology and single-cell isolation and seque ....Revealing bat antibody recognition mechanism against bat-borne viruses. Bats act as asymptomic reservoir hosts for numerous zoonotic viruses that are lethal in humans, indicating that the bat immune system can control these viruses. However, little is known about bat immunity including how bat antibodies recognise bat-borne viruses. This project aims to study bat anti-viral antibodies by utilising innovative protein engineering, cutting-edge cryo-EM technology and single-cell isolation and sequencing. The project seeks to uncover bat-borne zoonotic virus glycoprotein architecture and reveal how bat antibodies function to inhibit viral infection. Expected outcomes will be new insight and tools to combat emerging and yet to emerge pathogens, enabling pandemic preparedness and increasing global biosecurity.
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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
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
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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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
The viral fusosome: a modular machinery for cargo delivery to target cells. The delivery of proteins, RNA and DNA into cells is a critical process in normal cellular biology, virus infection and biotechnology applications such as gene editing. Enveloped viruses achieve this maneuver with exquisite efficiency and specificity using a complex machinery mediating their fusion with cellular membranes for stealth genome delivery. Remarkably, all characterised viral fusion proteins belong to only 3 cla ....The viral fusosome: a modular machinery for cargo delivery to target cells. The delivery of proteins, RNA and DNA into cells is a critical process in normal cellular biology, virus infection and biotechnology applications such as gene editing. Enveloped viruses achieve this maneuver with exquisite efficiency and specificity using a complex machinery mediating their fusion with cellular membranes for stealth genome delivery. Remarkably, all characterised viral fusion proteins belong to only 3 classes defined >16 years ago and sharing surprisingly conserved mechanisms. We identified a novel class of fusion proteins with unique architecture in ubiquitous insect viruses. The Project will elucidate the structural and functional hallmarks of this fusion machinery providing a platform for its engineering.Read moreRead less