Drug discovery and structural biology by NMR spectroscopy. This project aims to extend the use of nuclear magnetic resonance (NMR) spectroscopy in rational drug development and protein structure analysis. A new chemical labelling approach provides detailed three-dimensional structure information of large protein-ligand complexes, needed for structure-based lead-compound development. New chemical and paramagnetic lanthanide tags for site-specific dual labelling of proteins will enhance this techn ....Drug discovery and structural biology by NMR spectroscopy. This project aims to extend the use of nuclear magnetic resonance (NMR) spectroscopy in rational drug development and protein structure analysis. A new chemical labelling approach provides detailed three-dimensional structure information of large protein-ligand complexes, needed for structure-based lead-compound development. New chemical and paramagnetic lanthanide tags for site-specific dual labelling of proteins will enhance this technology, which will assess target-drug interactions by in-cell electron paramagnetic resonance (EPR) spectroscopy. The techniques offer scope for accelerated drug development in the pharmaceutical industries.Read moreRead less
New methods for structural biology and drug discovery by nuclear magnetic resonance spectroscopy. Paramagnetic lanthanide tags offer fresh opportunities in structural biology and for rational drug design. Novel nuclear magnetic resonance (NMR) spectroscopy techniques will selectively detect the NMR signals from protein regions marked by paramagnetic lanthanides, accelerating the structure analysis of protein-ligand complexes. New lanthanide tags will bind to phosphoserine and selenocysteine resi ....New methods for structural biology and drug discovery by nuclear magnetic resonance spectroscopy. Paramagnetic lanthanide tags offer fresh opportunities in structural biology and for rational drug design. Novel nuclear magnetic resonance (NMR) spectroscopy techniques will selectively detect the NMR signals from protein regions marked by paramagnetic lanthanides, accelerating the structure analysis of protein-ligand complexes. New lanthanide tags will bind to phosphoserine and selenocysteine residues site-specifically introduced into proteins. These tags will also enable accurate distance measurements by electron paramagnetic resonance (EPR) spectroscopy in large, biologically important protein systems hitherto not amenable to detailed structural studies and in proteins undergoing conformational changes. Read moreRead less
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.
New methods for structure analysis of proteins and protein interactions. This project will advance nuclear magnetic resonance (NMR) technologies pioneered at the Australian National University which employ site-specific attachment of paramagnetic metal tags to proteins. A new and diverse set of strategies will dramatically extend the range of applications to targets of interest in the fight against cancer and bacterial infections.
Structure function analysis of the NusA-RNA polymerase interaction. Genes must be turned on at the right time, at the correct level in the appropriate cell in all organisms. This project will determine the role of an essential component of the process in bacteria called NusA. The results will apply to bacteria as well as higher organisms, and also have the potential to identify a new antibiotic target.
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.