Structural studies of host-pathogen interactions. The host-pathogen interface represents a major frontier for biomedical and biotechnological applications. This project aims to understand at the atomic level two such interfaces. In the first instance, the project will elucidate the molecular basis for inhibition of premature host cell death by poxviruses, in particular vaccinia and variola virus, the causative agent of smallpox. In the second instance, the aim is to understand how defensins, a ....Structural studies of host-pathogen interactions. The host-pathogen interface represents a major frontier for biomedical and biotechnological applications. This project aims to understand at the atomic level two such interfaces. In the first instance, the project will elucidate the molecular basis for inhibition of premature host cell death by poxviruses, in particular vaccinia and variola virus, the causative agent of smallpox. In the second instance, the aim is to understand how defensins, a major class of host defence molecules, recognise microbial targets such as fungi, and exert a potent antimicrobial effect. Understanding the precise molecular mechanisms operating at both these host-pathogen interfaces this will provide novel avenues for the design of antiviral and antimicrobial agents.Read moreRead less
The ins and outs of HIV biology. This project aims to delineate the fundamental mechanisms that regulate the production of HIV and the ability of HIV to cause AIDS in infected patients. It will utilise state-of-the-art technologies to unearth new clues that govern the biology of HIV, with the ultimate goal to develop novel vaccine and treatment strategies against HIV.
Complement evasion strategies of malaria parasites. Pathogens have evolved to protect themselves from deleterious effects of host immune attack. Malaria is one of the most widespread parasitic diseases, yet evasion strategies employed by these parasites are unknown. This project will aim to understand how malaria parasites exploit the innate immune system for successful human infection.
How Bacteria Fold Virulence Factors to Cause Disease. Bacteria use folding enzymes to assemble proteins essential for cell integrity and pathogenicity. These foldases include the Disulphide bridge proteins, which catalyse the introduction of disulfide bonds. This project will study two important human pathogens, Salmonella Typhimurium and uropathogenic Escherichia coli, to address the fundamental and poorly understood questions of diversity of Dsb networks across bacterial pathogens and the role ....How Bacteria Fold Virulence Factors to Cause Disease. Bacteria use folding enzymes to assemble proteins essential for cell integrity and pathogenicity. These foldases include the Disulphide bridge proteins, which catalyse the introduction of disulfide bonds. This project will study two important human pathogens, Salmonella Typhimurium and uropathogenic Escherichia coli, to address the fundamental and poorly understood questions of diversity of Dsb networks across bacterial pathogens and the role of these foldases in virulence. The research will reveal how bacterial virulence factors are folded, identify novel targets for therapeutic intervention and provide the basis for structure-based design on new antimicrobials in the future. Read moreRead less
Unraveling autotransporter function in bacterial aggregates and biofilms. Autotransporters are a large family of bacterial proteins that play a central role in pathogenesis. They promote the formation of cell clusters and biofilms, which are mechanisms for bacterial resistance to host immune factors and antibiotics. Currently, the precise mode of action of autotransporters is unknown. This project will examine the interplay between the structure and function of key autotransporter proteins. It ....Unraveling autotransporter function in bacterial aggregates and biofilms. Autotransporters are a large family of bacterial proteins that play a central role in pathogenesis. They promote the formation of cell clusters and biofilms, which are mechanisms for bacterial resistance to host immune factors and antibiotics. Currently, the precise mode of action of autotransporters is unknown. This project will examine the interplay between the structure and function of key autotransporter proteins. It is expected that the outcomes of this research will establish how these proteins mediate aggregation and biofilm formation. It may also provide three-dimensional structures of proteins that are strongly immunogenic and may represent targets for future vaccine design, as well as identify molecules that inhibit autotransporter function.Read moreRead less
Highly ordered and tunable extracellular DNA micro- and nanopatterns for investigating the attachment mechanisms of pseudomonas aeruginosa to surfaces. Preventing infectious bacteria from colonising artificial surfaces is a major scientific challenge. New engineered surfaces will be designed to better understand how the important pathogen Pseudomonas aeruginosa sticks to surfaces, facilitating new ways of reducing infections acquired from the surface of, for example, medical devices.
The regulation of anti-viral immunity by host and viral proteins. Anti-viral immunity is initially triggered when specific immune sensors detect viral components within the cell. This project will use a combined functional/structural approach to investigate the specifics of immune activation by a pivotal immune sensor and use this information to understand how influenza A sabotages this specific immune response.
Discovery Early Career Researcher Award - Grant ID: DE190100304
Funder
Australian Research Council
Funding Amount
$416,092.00
Summary
Understanding intramolecular regulation of ubiquitin enzymes. This project aims to combine structural, biophysical and functional studies to characterise how ubiquitin enzymes are regulated. Ubiquitination controls essential cellular pathways in all eukaryotes and this project expects to generate new knowledge regarding the vital regulation of this process. This project expects to develop broadly applicable techniques for investigating protein conformation and self-association as a means of cont ....Understanding intramolecular regulation of ubiquitin enzymes. This project aims to combine structural, biophysical and functional studies to characterise how ubiquitin enzymes are regulated. Ubiquitination controls essential cellular pathways in all eukaryotes and this project expects to generate new knowledge regarding the vital regulation of this process. This project expects to develop broadly applicable techniques for investigating protein conformation and self-association as a means of controlling catalytic activity. The project should significantly increase understanding of several modes of regulation of ubiquitin ligase catalytic activity, and how this controls a myriad of cellular processes. The project will lay the foundation for applied research anti-viral compounds, plant anti-fungals and cancer therapies.Read moreRead less
Structure-based design of inhibitors of HIV-1 integrase. This project will produce compounds that block human immunodeficiency virus (HIV) replication. These compounds will benefit the 17000 Australians and more than 34 million people worldwide who are currently suffering with this terrible disease.
How auto-transporter proteins mediate bacterial interactions. This project aims to investigate the structure-function relationships that underpin key auto-transporter roles in bacterial cell adhesion, aggregation and biofilm formation. Auto-transporter proteins are extremely common in bacteria where they play a central role in controlling bacterial interactions with other bacteria, with human cells, and with surfaces. This project will define the molecular mechanisms underlying these processes. ....How auto-transporter proteins mediate bacterial interactions. This project aims to investigate the structure-function relationships that underpin key auto-transporter roles in bacterial cell adhesion, aggregation and biofilm formation. Auto-transporter proteins are extremely common in bacteria where they play a central role in controlling bacterial interactions with other bacteria, with human cells, and with surfaces. This project will define the molecular mechanisms underlying these processes. This will have significant benefits, such as providing the basis for the development of approaches to block auto-transporter functions that contribute to the establishment of persistent and difficult to treat bacterial infections.Read moreRead less