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
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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Viral allies: shedding light on beneficial insect viruses. Baculoviruses are rare examples of viruses recognised for their positive impact on human activities. These viruses infect a broad range of insects and have been widely used in biological research, biotechnology and agricultural pest control. This Project aims to elucidate the structure and assembly of these beneficial viruses using advanced structural, biochemical and imaging approaches. The Project is expected to generate high-resolutio ....Viral allies: shedding light on beneficial insect viruses. Baculoviruses are rare examples of viruses recognised for their positive impact on human activities. These viruses infect a broad range of insects and have been widely used in biological research, biotechnology and agricultural pest control. This Project aims to elucidate the structure and assembly of these beneficial viruses using advanced structural, biochemical and imaging approaches. The Project is expected to generate high-resolution models that define hallmarks of a new viral lineage, a significant breakthrough in our understanding of the virosphere, and underpin the future development of innovative baculovirus-based technologies such as selective bioinsecticides for the sustainable control of invasive insects.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
Discovery Early Career Researcher Award - Grant ID: DE200100977
Funder
Australian Research Council
Funding Amount
$419,016.00
Summary
How ecology shapes the viromes of wild birds. This project will reveal the host factors associated with the diversity, evolution and dynamics of viruses using state-of-the-art metatranscriptomics in Australian wild birds. The structure of virus communities and their associated ecological drivers in wild animal hosts remain a black-box, even though they are the largest source of viral diversity in nature. This project expects to generate key insights into host-associated drivers of viral communit ....How ecology shapes the viromes of wild birds. This project will reveal the host factors associated with the diversity, evolution and dynamics of viruses using state-of-the-art metatranscriptomics in Australian wild birds. The structure of virus communities and their associated ecological drivers in wild animal hosts remain a black-box, even though they are the largest source of viral diversity in nature. This project expects to generate key insights into host-associated drivers of viral community dynamics and the subsequent effect of anthropogenic factors such as urbanisation and poultry production. Identifying host factors that affect viral ecology in wild birds will constitute a cornerstone in understanding the emergence of virulent viruses and/or their spread to poultry or humansRead 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
Why certain viruses don't get along in mosquitoes. The molecular mechanism. The overall goal of this project is to obtain an understanding of how certain insect-only viruses make mosquitoes incapable of transmitting diseases. These viruses, called insect-specific flaviviruses, can be employed as biocontrol agents for mosquito-borne human and veterinary diseases. However as it is currently unknown how exactly they affect mosquitoes, the safety and efficacy of their use can't be predicted. The pro ....Why certain viruses don't get along in mosquitoes. The molecular mechanism. The overall goal of this project is to obtain an understanding of how certain insect-only viruses make mosquitoes incapable of transmitting diseases. These viruses, called insect-specific flaviviruses, can be employed as biocontrol agents for mosquito-borne human and veterinary diseases. However as it is currently unknown how exactly they affect mosquitoes, the safety and efficacy of their use can't be predicted. The proposed project will dissect the very intricate mechanisms of interactions between insect-specific flaviviruses and mosquitoes and explain how exactly they prevent disease transmission. It should generate novel fundamental knowledge, implement innovative methodologies and provide training for students and junior scientist. Read moreRead less