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
Bioactive Peptides as Pharmacological Tools and Novel Drug Leads. Bioactive peptides are produced by all organisms and play numerous critical physiological roles, including in cellular communication, host defence and capture of prey. Peptides have huge potential as tools for studying roles of signalling pathways and as novel drugs due to their high affinity and selectivity for various therapeutically relevant targets. However their use has been limited by poor in vivo stability. This project is ....Bioactive Peptides as Pharmacological Tools and Novel Drug Leads. Bioactive peptides are produced by all organisms and play numerous critical physiological roles, including in cellular communication, host defence and capture of prey. Peptides have huge potential as tools for studying roles of signalling pathways and as novel drugs due to their high affinity and selectivity for various therapeutically relevant targets. However their use has been limited by poor in vivo stability. This project is focused on studying structural features of a range of peptides and their contributions to both activity and to resistance against degradation, with the aim to develop stabilised bioactive peptide sequences for in vivo applications, allowing the full potential of peptides as drugs to be realised.Read moreRead less
Mathematical models of diseases with complex transmission routes. This project aims to model diseases that spread via a mixture of routes including food, water, the environment, and direct spread between individuals. Key diseases include: avian influenza, which causes massive disruption to the poultry industry; gastroenteritis, which costs Australia $1,250 million each year; and leptospirosis, which causes one million severe illnesses each year globally. This project will develop mathematical a ....Mathematical models of diseases with complex transmission routes. This project aims to model diseases that spread via a mixture of routes including food, water, the environment, and direct spread between individuals. Key diseases include: avian influenza, which causes massive disruption to the poultry industry; gastroenteritis, which costs Australia $1,250 million each year; and leptospirosis, which causes one million severe illnesses each year globally. This project will develop mathematical and statistical tools to better estimate risk, analyse outbreak data, and provide guidance for disease control. This research will improve policy and enhance our ability to respond to disease outbreaks.Read moreRead less
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.