Discovery Early Career Researcher Award - Grant ID: DE140101493
Funder
Australian Research Council
Funding Amount
$368,720.00
Summary
A glycomics approach towards the discovery of novel markers of virus transmission by mosquitoes. The incidence of human and animal diseases caused by mosquito-borne pathogens has increased at an alarming rate globally. This project utilises state-of-the-art glyco-virological approaches and an arbovirus model system to identify new markers associated with virus transmission by mosquitoes. Markers associated with transmission will be identified by establishing global glycan and lectin profiles of ....A glycomics approach towards the discovery of novel markers of virus transmission by mosquitoes. The incidence of human and animal diseases caused by mosquito-borne pathogens has increased at an alarming rate globally. This project utilises state-of-the-art glyco-virological approaches and an arbovirus model system to identify new markers associated with virus transmission by mosquitoes. Markers associated with transmission will be identified by establishing global glycan and lectin profiles of the cells derived from a major mosquito species. This will fill a significant gap in our knowledge of basic transmission mechanisms in mosquitoes. The research strategy is a world-first and the institute is an international leader in this area. Read moreRead less
Defining the evolution of pathogen virulence to enhance rabbit biocontrol. Rabbits impose a major economic and ecological burden on Australia. Biocontrols involving viruses are the best means to regulate rabbit populations, although they often have transient effectiveness. It is therefore essential to determine why some viruses retain the high virulence essential for effective biocontrol, while others are consistently benign. Through bioinformatic and experimental studies of two rabbit viruses w ....Defining the evolution of pathogen virulence to enhance rabbit biocontrol. Rabbits impose a major economic and ecological burden on Australia. Biocontrols involving viruses are the best means to regulate rabbit populations, although they often have transient effectiveness. It is therefore essential to determine why some viruses retain the high virulence essential for effective biocontrol, while others are consistently benign. Through bioinformatic and experimental studies of two rabbit viruses with markedly different virulence, Rabbit Haemorrhagic Disease virus (high virulence) and Australian rabbit calicivirus (low virulence), this project will determine the molecular mechanisms that control virulence and the factors that shape virulence evolution. Ultimately, this research will help improve rabbit biocontrol in Australia.Read moreRead less
Anthocyanin Inhibitors to the Influenza Virus. The increasing resistance of circulating influenza strains to current anti-viral inhibitors has prompted an investigation to screen, design, synthesize and evaluate a new class of natural product based inhibitors to the virus employing novel and innovative mass spectrometry, computational and structural approaches. Preliminary studies reveal they offer benefits in terms of a different mode of binding to influenza neuraminidase, remote from many know ....Anthocyanin Inhibitors to the Influenza Virus. The increasing resistance of circulating influenza strains to current anti-viral inhibitors has prompted an investigation to screen, design, synthesize and evaluate a new class of natural product based inhibitors to the virus employing novel and innovative mass spectrometry, computational and structural approaches. Preliminary studies reveal they offer benefits in terms of a different mode of binding to influenza neuraminidase, remote from many known resistance mutations, and may have specific practicality against N1 neuraminidase in H1N1 and H5N1 viruses responsible for all pandemics of the 20th and 21st centuries. The research will enable the potential of these inhibitors to be fully assessed at the molecular level for the first time.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
From shape to function: how structured RNA defines insect flaviviruses. The goal of this project is to obtain an understanding of how insect-specific flaviviruses (ISFs) utilise viral noncoding RNAs to enable their replication in mosquitoes. These viruses only replicate in mosquitoes, and not in humans or animals. They can be employed as the biocontrol agents for mosquito-borne diseases as they make mosquitoes incapable of disease transmission. However, it is currently unknown how exactly insect ....From shape to function: how structured RNA defines insect flaviviruses. The goal of this project is to obtain an understanding of how insect-specific flaviviruses (ISFs) utilise viral noncoding RNAs to enable their replication in mosquitoes. These viruses only replicate in mosquitoes, and not in humans or animals. They can be employed as the biocontrol agents for mosquito-borne diseases as they make mosquitoes incapable of disease transmission. However, it is currently unknown how exactly insect-specific flaviviruses affect mosquitoes and this information is vital for informed design of ISF-based interventions. The project will generate new knowledge on functions of noncoding RNAs in ISFs that are hypothesised to have immunomodulatory role in mosquitoes. It will also train students and ECRs.Read moreRead less
Detection of imported exotic strains of West Nile virus for national biosecurity surveillance. West Nile virus (WNV) is transmitted by mosquitoes and causes a fatal disease of the brain in animals and humans. WNV is currently exotic to this country, however a closely related, but benign cousin of this virus (Kunjin) can be found in Northern Australia. Currently it is very difficult to differentiate between infections with WNV and Kunjin using standard laboratory tests, therefore it will be diff ....Detection of imported exotic strains of West Nile virus for national biosecurity surveillance. West Nile virus (WNV) is transmitted by mosquitoes and causes a fatal disease of the brain in animals and humans. WNV is currently exotic to this country, however a closely related, but benign cousin of this virus (Kunjin) can be found in Northern Australia. Currently it is very difficult to differentiate between infections with WNV and Kunjin using standard laboratory tests, therefore it will be difficult for public health officials to detect WNV if it is introduced to Australia. In this project we aim to develop more accurate laboratory tests to detect infections with the deadly, exotic WNV using new strategies. 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
Australian Laureate Fellowships - Grant ID: FL170100022
Funder
Australian Research Council
Funding Amount
$3,402,903.00
Summary
Redefining virus ecology and evolution. This project aims to employ novel genomic analyses of viruses from Australian fauna to resolve major questions in RNA virus ecology and evolution, and is expected to reveal the basic processes that shape the virosphere, determine how viruses jump species to emerge and cause disease in new hosts, and how viruses evolve new levels of virulence. The research will provide a new understanding of how viruses evolve and contribute to global ecosystems and develop ....Redefining virus ecology and evolution. This project aims to employ novel genomic analyses of viruses from Australian fauna to resolve major questions in RNA virus ecology and evolution, and is expected to reveal the basic processes that shape the virosphere, determine how viruses jump species to emerge and cause disease in new hosts, and how viruses evolve new levels of virulence. The research will provide a new understanding of how viruses evolve and contribute to global ecosystems and develop new bioinformatics tools to identify and analyse highly divergent genome sequences through studying meta-transcriptomic data from diverse animal phyla, from prokaryotes and basal eukaryotes, from iconic native mammalian species and their major invasive pests. The benefits provided will include determining the viromes of native and invasive species and enhancing the efforts to protect iconic Australian species from infectious disease.Read moreRead less
Enhancement of monopartite geminivirus pathogenicity by satellite DNA beta encoded betaC1 protein: the role of host factors. Australian incursions of geminiviruses are uncontrollable due to their unique mode of spread by whiteflies. The first incursion in Darwin in 1970 has spread to Far Northern Queensland. The second in SE Queensland in 2006 is estimated to cause $500 million loss to horticulture. Our $2 billion cotton industry is threatened by cotton leaf curl diseases from South Asia, where ....Enhancement of monopartite geminivirus pathogenicity by satellite DNA beta encoded betaC1 protein: the role of host factors. Australian incursions of geminiviruses are uncontrollable due to their unique mode of spread by whiteflies. The first incursion in Darwin in 1970 has spread to Far Northern Queensland. The second in SE Queensland in 2006 is estimated to cause $500 million loss to horticulture. Our $2 billion cotton industry is threatened by cotton leaf curl diseases from South Asia, where DNA beta enhances virus replication and disease severity. DNA beta has the potential to enter Australia with several different geminiviruses and to spread into others by co-infection, which requires research on detection and pathogenesis of DNA beta.Read moreRead less
Microcrystallography of spheroids: crystalline armours of insect viruses. The proposed project will provide fundamental insights into the organisation of ultra-stable armours protecting insect viruses. This will open novel avenues for the development of highly efficient and specific bioinsectides as well as innovative tools such as natural microparticles for improved vaccines.
The techniques used in this project are at the frontier of imaging techniques and will establish a national expertise i ....Microcrystallography of spheroids: crystalline armours of insect viruses. The proposed project will provide fundamental insights into the organisation of ultra-stable armours protecting insect viruses. This will open novel avenues for the development of highly efficient and specific bioinsectides as well as innovative tools such as natural microparticles for improved vaccines.
The techniques used in this project are at the frontier of imaging techniques and will establish a national expertise in X-ray micro-crystallography. This will contribute to the optimal use of the $8-million microfocus beamline of the newly built Australian Synchrotron enabling breakthroughs such as the structures of membrane receptors for hormone and neurotransmitter with major implications for drug development.Read moreRead less