Discovery Early Career Researcher Award - Grant ID: DE220100185
Funder
Australian Research Council
Funding Amount
$438,712.00
Summary
Decoding the evolution of killer T cell immunity across human lifetime. The immune system is a potent weapon for protection against pathogens. T cells have a central role as their receptors monitor the body for threats. The thymus (organ) educates receptors to discriminate between healthy and infected cells. Receptor diversity and T cell strength change throughout human life. This project aims to unravel how T cells gain and lose optimal receptors and strength. The aims are to understand 1) The ....Decoding the evolution of killer T cell immunity across human lifetime. The immune system is a potent weapon for protection against pathogens. T cells have a central role as their receptors monitor the body for threats. The thymus (organ) educates receptors to discriminate between healthy and infected cells. Receptor diversity and T cell strength change throughout human life. This project aims to unravel how T cells gain and lose optimal receptors and strength. The aims are to understand 1) The role of thymic education in diversifying receptors 2) Whether gradual loss of thymic education affects receptor diversity 3) The molecular mechanisms underlying T cell strength. The project is essential for understanding how optimal T cell immunity is formed, critical if we wish to harness this to improve healthy aging.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE210101145
Funder
Australian Research Council
Funding Amount
$414,662.00
Summary
Investigating novel neurobiological mechanisms in rabies infection. This project aims to better understand the biology and functioning of the nervous system using an innovative multi-disciplinary approach informed by the rabies virus. The study intends to identify the molecular mechanism responsible for self-destruction in neurons. The project aims to gain this new knowledge by investigating the novel natural ability of rabies virus to subdue self-destruction mechanism in neurons. The principal ....Investigating novel neurobiological mechanisms in rabies infection. This project aims to better understand the biology and functioning of the nervous system using an innovative multi-disciplinary approach informed by the rabies virus. The study intends to identify the molecular mechanism responsible for self-destruction in neurons. The project aims to gain this new knowledge by investigating the novel natural ability of rabies virus to subdue self-destruction mechanism in neurons. The principal benefit is the gain of detailed knowledge about a fundamental biological mechanism at the intersection of neurobiology and virology. This has the potential to inform future research in areas such as the maintenance of neuronal health in ageing and better control of rabies infections. 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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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
Defining the antiviral effects of Wolbachia in Aedes aegypti mosquitoes. Mosquitoes that carry a bacterium called Wolbachia do not transmit human pathogenic viruses. These mosquitoes are being developed as a biocontrol tool to prevent mosquito-borne diseases. This project aims to define the molecular basis for virus inhibition by Wolbachia. Using unique biological tools including mosquitoes carrying different strains of Wolbachia that do or do not inhibit dengue virus, the project will define ho ....Defining the antiviral effects of Wolbachia in Aedes aegypti mosquitoes. Mosquitoes that carry a bacterium called Wolbachia do not transmit human pathogenic viruses. These mosquitoes are being developed as a biocontrol tool to prevent mosquito-borne diseases. This project aims to define the molecular basis for virus inhibition by Wolbachia. Using unique biological tools including mosquitoes carrying different strains of Wolbachia that do or do not inhibit dengue virus, the project will define how Wolbachia modifies its host to create an antiviral state. The findings will provide insight into how viral pathogens can be suppressed in insect hosts. This may guide future viral disease intervention strategies for diverse areas afflicted by insect-borne viral disease, including human health and agriculture.Read moreRead less
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
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
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