Functional characterisation of poly-histidine triad proteins. This project aims to understand the role and function of a novel family of surface proteins produced by Streptococci. These so-called polyhistidine triad proteins are known to contribute to capacity to cause disease in animals and humans, but we need to know how they work, as they may be excellent targets for novel drugs or vaccines.
Novel perspectives on the function of AB5 toxin B subunits in pathogenic bacterial. AB5 toxins are produced by bacteria that cause important diseases in humans and livestock. This project tests the hypothesis that the components of the toxins responsible for binding to host cells and tissues also directly contribute to cellular damage, thereby providing a better understanding of how AB5 toxin-producing bacteria cause disease.
Bacterial poly-histidine triad proteins. The poly-histidine triad (Pht) proteins are a poorly characterised family of surface proteins expressed by the genus Streptococcus and other Gram-positive genera. Recent studies suggest an important role for Pht proteins in survival of these bacteria in low zinc (Zn) environments. The project hypothesis is that Pht proteins specifically recruit Zn from the extracellular environment and somehow make it available to ATP binding cassette (ABC) transport syst ....Bacterial poly-histidine triad proteins. The poly-histidine triad (Pht) proteins are a poorly characterised family of surface proteins expressed by the genus Streptococcus and other Gram-positive genera. Recent studies suggest an important role for Pht proteins in survival of these bacteria in low zinc (Zn) environments. The project hypothesis is that Pht proteins specifically recruit Zn from the extracellular environment and somehow make it available to ATP binding cassette (ABC) transport systems located in the bacterial plasma membrane, beneath the cell wall, facilitating Zn uptake by the bacterium. The aim of this project is to conduct comprehensive molecular characterization of the interactions between Pht proteins, Zn and ABC transporters, and the role of the histidine triad motifs in these interactions.Read moreRead less
Host-pathogen interactions: the role of mimicry. The proposed research program, using a combination of structure and functional analysis will provide insight into the mechanism of nucleotide hydrolysis by the enzymes NTPDases. This study will not only improve our fundamental understanding of NTPDase action but could lead to the rational design of antimicrobials.
Designing effective Gram negative bacterial vaccines. There is a need for the development of novel vaccines for use in animals and humans. This project will to address this need by studying the functions of bacterial 'blebs' as potent inducers of the host immune system and by developing these nano-sized particles for use as safe and cost-effective vaccine candidates.
Generation and Exploitation of Fermentation Products in the Chemical Synthesis of Biologically Active Compounds with Therapeutic Potential. Dramatic developments in biotechnology have provided access to genetically engineered micro-organisms capable of effecting unusual transformations so as to form novel compounds of great value in chemical synthesis. This project will combine the powers of biotechnology with those of chemical synthesis to produce compounds that have therapeutic potential in th ....Generation and Exploitation of Fermentation Products in the Chemical Synthesis of Biologically Active Compounds with Therapeutic Potential. Dramatic developments in biotechnology have provided access to genetically engineered micro-organisms capable of effecting unusual transformations so as to form novel compounds of great value in chemical synthesis. This project will combine the powers of biotechnology with those of chemical synthesis to produce compounds that have therapeutic potential in the treatment of Alzheimer's disease, cancer and viral infections.Read moreRead less
Dissociation of a Tetrameric Enzyme with Interface-Targeted Peptides. With antibiotic resistance on the rise, there is an urgent need to develop new antibiotics and an equally urgent need to characterise new antibiotic targets. One such target is dihydrodipicolinate synthase (DHDPS) which catalyses the critical step in lysine and cell wall biosynthesis in bacteria. This proposal aims to generate new drugs targeting DHDPS for effective and rapid treatment of bacterial infections, including gastro ....Dissociation of a Tetrameric Enzyme with Interface-Targeted Peptides. With antibiotic resistance on the rise, there is an urgent need to develop new antibiotics and an equally urgent need to characterise new antibiotic targets. One such target is dihydrodipicolinate synthase (DHDPS) which catalyses the critical step in lysine and cell wall biosynthesis in bacteria. This proposal aims to generate new drugs targeting DHDPS for effective and rapid treatment of bacterial infections, including gastroenteritis. Recent statistics show that over 5 million Australians suffer from gastroenteritis each year and hospitalisation for this infection is nearly seven times higher for indigenous than non-indigenous children. Accordingly, this research has the potential to assure a healthier future for millions of Australians.Read moreRead less
Mapping cell wall and surface structures of Gram-positive cocci. The synthesis of the Gram-positive cell wall and protein transport are fundamental processes, the improved understanding of which will impact across a range of fields including microbiology, biochemistry and biotechnology, and the application and manipulation of Gram-positive bacteria in agriculture, industry and human health. In the long-term, the analysis of the Gram-positive ExPortal and cell wall will identify proteins that ma ....Mapping cell wall and surface structures of Gram-positive cocci. The synthesis of the Gram-positive cell wall and protein transport are fundamental processes, the improved understanding of which will impact across a range of fields including microbiology, biochemistry and biotechnology, and the application and manipulation of Gram-positive bacteria in agriculture, industry and human health. In the long-term, the analysis of the Gram-positive ExPortal and cell wall will identify proteins that may represent targets for therapeutic intervention. Additionally a precise understanding of the mechanisms of secretion of anchorless proteins will have an important impact in the biotechnology field, as new methodologies for the secretion of recombinant proteins of industrial value is a potential outcome.Read moreRead less
The protein O-glycosylation pathway of Neisseria: a model system for O-glycosylation of bacterial proteins with potential use in biotechnology. Proteins can be modified by the addition of sugar molecules. This process, called glycosylation, has been studied for some time in humans and other higher organisms, but is relatively new in the field of bacteria. This study will use the bacterium Neisseria as a model system for this process and work to harness the system for use in biotechnology.
Disrupting Chemical Communication in Bacteria: A Novel and Effective Antimicrobial Strategy. Due to increased application of antibiotics for disease control, many pathogenic bacteria have developed resistance to existing antimicrobials. The infections associated with the resistant bacteria incur a high cost in terms of human health, well being and health care costs. Thus, there is a clear need to develop new antimicrobials that have a novel mechanism of action. The technology proposed here has ....Disrupting Chemical Communication in Bacteria: A Novel and Effective Antimicrobial Strategy. Due to increased application of antibiotics for disease control, many pathogenic bacteria have developed resistance to existing antimicrobials. The infections associated with the resistant bacteria incur a high cost in terms of human health, well being and health care costs. Thus, there is a clear need to develop new antimicrobials that have a novel mechanism of action. The technology proposed here has the potential to deliver enormous health and social welfare benefits to the Australian population as well as commercial benefits to Australian industry, through provision of new, locally produced technologies for the control of bacterial virulence.Read moreRead less