Regulation of MHC-I and ICAM-1 by flavivirus, West Nile. This project investigates the intracellular signalling pathway responsible for the expression of genes which are critical to our immune response. We have demonstrated in a mouse model that high levels of expression of two of these genes in flavivirus encephalitis are associated with a survival advantage. We would expect this project to provide basic new information about the mechanisms of expression of these genes as well as information ab ....Regulation of MHC-I and ICAM-1 by flavivirus, West Nile. This project investigates the intracellular signalling pathway responsible for the expression of genes which are critical to our immune response. We have demonstrated in a mouse model that high levels of expression of two of these genes in flavivirus encephalitis are associated with a survival advantage. We would expect this project to provide basic new information about the mechanisms of expression of these genes as well as information about the interaction of this family of viruses, flavivirus with the host.Read moreRead less
Biological probes for understanding mammalian cellular transport mechanisms. Cellular components are moved around within cells by molecular motors. This fundamental transport mechanism depends on a network of tracks. Blocks in this cellular transport can result in a number of mammalian diseases, particularly within nerve cells. This project will increase our understanding of the mechanisms of cellular transport and, in particular, how molecular motors engage their cargo. This is essential ground ....Biological probes for understanding mammalian cellular transport mechanisms. Cellular components are moved around within cells by molecular motors. This fundamental transport mechanism depends on a network of tracks. Blocks in this cellular transport can result in a number of mammalian diseases, particularly within nerve cells. This project will increase our understanding of the mechanisms of cellular transport and, in particular, how molecular motors engage their cargo. This is essential groundwork for the development of drugs that target this transport mechanism.Read moreRead less
Using viral inhibitors to understand the regualtion of apoptosis. Apoptosis is a form of cell death that is critical for the development and well-being of multicellular organisms. The activity of Bak or Bax, two members of the Bcl-2 family, are essential for apoptosis to proceed, but how the activity of these two proteins is regulated is unclear. Many viruses encode inhibitors of apoptosis and the project will make use of two novel viral inhibitors that specifically target Bak. The project aims ....Using viral inhibitors to understand the regualtion of apoptosis. Apoptosis is a form of cell death that is critical for the development and well-being of multicellular organisms. The activity of Bak or Bax, two members of the Bcl-2 family, are essential for apoptosis to proceed, but how the activity of these two proteins is regulated is unclear. Many viruses encode inhibitors of apoptosis and the project will make use of two novel viral inhibitors that specifically target Bak. The project aims to determine how the Bak inhibitors function and to provide valuable insights into the normal mechanisms regulating Bak activity.Read moreRead less
Regulation of human immunodeficiency virus type 1 (HIV-1) replication by viral and cellular proteins. Using a mouse model, human cells will be treated with a very powerful antiviral protein using a gene therapy approach so as to block the human immunodeficiency virus (HIV) from growing. By learning how this antiviral protein works, this project will assist in the development of new strategies to treat HIV infection.
The fate of single virus particles during infection. This project applies innovative imaging techniques to elucidate the logistics of cellular function. Establishing a cutting-edge technology platform will spawn discovery and research creativity in fundamental science, as well as applications in biomedical and biotechnology research disciplines. We will foster a highly skilled workforce, an essential asset for maintaining and enhancing Australia's reputation and capability as a leader in researc ....The fate of single virus particles during infection. This project applies innovative imaging techniques to elucidate the logistics of cellular function. Establishing a cutting-edge technology platform will spawn discovery and research creativity in fundamental science, as well as applications in biomedical and biotechnology research disciplines. We will foster a highly skilled workforce, an essential asset for maintaining and enhancing Australia's reputation and capability as a leader in research excellence.Read moreRead less
Regulation of DNA synthesis and host evasion by Lentivirus Capsids. This project aims to investigate how a type of virus, exemplified by HIV, can synthesise DNA in the cytoplasm of a host cell, without triggering the cell’s innate immunity when DNA is detected outside the nucleus. It expects to advance understanding of the role of the virus’ protein shell in regulating DNA synthesis during infection. The project outcomes should include enhanced capacity for fundamental virus and cell biology re ....Regulation of DNA synthesis and host evasion by Lentivirus Capsids. This project aims to investigate how a type of virus, exemplified by HIV, can synthesise DNA in the cytoplasm of a host cell, without triggering the cell’s innate immunity when DNA is detected outside the nucleus. It expects to advance understanding of the role of the virus’ protein shell in regulating DNA synthesis during infection. The project outcomes should include enhanced capacity for fundamental virus and cell biology research in Australia. The project anticipates contributing to new tools for delivering genes to cells, benefiting therapeutic and biotechnology applications.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
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
In vivo assembly and virulence of poxvirus infectious crystals. Widespread insect viruses have evolved unique infectious forms called crystalline armours. This project will use innovative biophysical approaches to understand how these virus-containing crystals assemble and package viruses and contribute to virulence as a rational basis for improved bioinsecticides and novel microparticles for biotechnological applications.
Discovery Early Career Researcher Award - Grant ID: DE170100783
Funder
Australian Research Council
Funding Amount
$372,000.00
Summary
Structural basis of paramyxovirus host cell entry. This project aims to investigate interactions between paramyxoviruses and host cell receptors and the mechanisms underlying fusion activation at a molecular level. Paramyxoviruses include economically important human and animal pathogens. Two viral proteins are key to infection: an attachment protein for the interaction with host receptors, and a fusion protein for fusion of viral and cellular membranes. The project is anticipated to discover ge ....Structural basis of paramyxovirus host cell entry. This project aims to investigate interactions between paramyxoviruses and host cell receptors and the mechanisms underlying fusion activation at a molecular level. Paramyxoviruses include economically important human and animal pathogens. Two viral proteins are key to infection: an attachment protein for the interaction with host receptors, and a fusion protein for fusion of viral and cellular membranes. The project is anticipated to discover general principles of how paramyxoviruses infect host cells, which should advance fundamental understanding of viral infection strategies and may identify strategies for rational design of inhibitors targeting host-cell entry of multiple paramyxoviruses.Read moreRead less