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
Salmonella in poultry: improving vaccine efficacy . The central aim of this project is to increase the antigenicity of aroA mutant Salmonella Typhimurium vaccines, in particular Bioproperties’ Vaxsafe® ST. Increased antigenicity will affect the gut microbiota and stimulate a stronger host immune response improving vaccine efficacy and the duration of protection against S. Typhimurium in poultry. This will ultimately reduce bacterial loads in the farm environment, mitigate downstream contaminatio ....Salmonella in poultry: improving vaccine efficacy . The central aim of this project is to increase the antigenicity of aroA mutant Salmonella Typhimurium vaccines, in particular Bioproperties’ Vaxsafe® ST. Increased antigenicity will affect the gut microbiota and stimulate a stronger host immune response improving vaccine efficacy and the duration of protection against S. Typhimurium in poultry. This will ultimately reduce bacterial loads in the farm environment, mitigate downstream contamination of the food supply chain, and reduce the number of human salmonellosis cases.Read moreRead less
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
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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Safeguarding Australia against vector-borne disease bio-incursions. Traditional diagnostic tests limited by their accuracy and ability to detect more than a few pathogens at one time, presents a major hurdle to protecting Australia's companion animals from a plethora of exotic and emerging vector-borne diseases (VBD). Many of these diseases also pose a major risk to public health. This project aims to develop, validate and verify a highly accurate, cost-effective, portable metabarcoding diagnost ....Safeguarding Australia against vector-borne disease bio-incursions. Traditional diagnostic tests limited by their accuracy and ability to detect more than a few pathogens at one time, presents a major hurdle to protecting Australia's companion animals from a plethora of exotic and emerging vector-borne diseases (VBD). Many of these diseases also pose a major risk to public health. This project aims to develop, validate and verify a highly accurate, cost-effective, portable metabarcoding diagnostic test capable of detecting known, emerging and novel parasitic, bacterial and viral VBD pathogens simultaneously, from clinical samples. The assay will represent a potential paradigm shift in the way VBD are tested, for the purpose of safeguarding Australia against VBD bio-incursions.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
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
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