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.
Quantitative Metagenomics. This project aims to revolutionize our view of the microbial world once more by transforming microbiome studies from relative counts of organisms to actual numbers of microbes. This project expects to impact all the microbiome studies that are being performed worldwide by unveiling the actual numbers of microbes. Expected outcomes of this project include new techniques to enumerate the number of bacteria in different environments and new approaches to measure gene expr ....Quantitative Metagenomics. This project aims to revolutionize our view of the microbial world once more by transforming microbiome studies from relative counts of organisms to actual numbers of microbes. This project expects to impact all the microbiome studies that are being performed worldwide by unveiling the actual numbers of microbes. Expected outcomes of this project include new techniques to enumerate the number of bacteria in different environments and new approaches to measure gene expression within individual bacteria in any environment that will be demonstrated with complex microbial communities. This should provide significant benefits because microbes affect every aspect of our lives and those effects are driven by how many microbes are present.Read moreRead less
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
Enhancement of monopartite geminivirus pathogenicity by satellite DNA beta encoded betaC1 protein: the role of host factors. Australian incursions of geminiviruses are uncontrollable due to their unique mode of spread by whiteflies. The first incursion in Darwin in 1970 has spread to Far Northern Queensland. The second in SE Queensland in 2006 is estimated to cause $500 million loss to horticulture. Our $2 billion cotton industry is threatened by cotton leaf curl diseases from South Asia, where ....Enhancement of monopartite geminivirus pathogenicity by satellite DNA beta encoded betaC1 protein: the role of host factors. Australian incursions of geminiviruses are uncontrollable due to their unique mode of spread by whiteflies. The first incursion in Darwin in 1970 has spread to Far Northern Queensland. The second in SE Queensland in 2006 is estimated to cause $500 million loss to horticulture. Our $2 billion cotton industry is threatened by cotton leaf curl diseases from South Asia, where DNA beta enhances virus replication and disease severity. DNA beta has the potential to enter Australia with several different geminiviruses and to spread into others by co-infection, which requires research on detection and pathogenesis of DNA beta.Read moreRead less
The basis of recognition and disposal of dysfunctional proteins by clusterin. When proteins become damaged they can precipitate. A blood protein called clusterin prevents precipitation of damaged proteins. Clusterin does this by forming complexes with the damaged proteins. Clusterin is the first blood protein known to do this. We will discover which parts of clusterin are responsible for this activity. We will also discover whether cells can take up and dispose of the complexes of clusterin and ....The basis of recognition and disposal of dysfunctional proteins by clusterin. When proteins become damaged they can precipitate. A blood protein called clusterin prevents precipitation of damaged proteins. Clusterin does this by forming complexes with the damaged proteins. Clusterin is the first blood protein known to do this. We will discover which parts of clusterin are responsible for this activity. We will also discover whether cells can take up and dispose of the complexes of clusterin and damaged proteins. This work is important because some diseases (eg, Alzheimers disease) involve the toxic effects of abnormal protein precipitation. Understanding how clusterin works may help in developing better treatments for these diseases.Read moreRead less
Investigating the evolution of innate and adaptive cellular immunity. This proposal aims to assess the impact of geographical and genetic isolation of the Australian Indigenous population on adaptive and innate immune systems. The project will use novel DNA sequencing approaches to generate the high resolution sequences of two genetic loci that regulate innate and adaptive immune responses, the major histocompatibility complex locus and the killer cell immunoglobulin-like receptor locus. In an i ....Investigating the evolution of innate and adaptive cellular immunity. This proposal aims to assess the impact of geographical and genetic isolation of the Australian Indigenous population on adaptive and innate immune systems. The project will use novel DNA sequencing approaches to generate the high resolution sequences of two genetic loci that regulate innate and adaptive immune responses, the major histocompatibility complex locus and the killer cell immunoglobulin-like receptor locus. In an initial screen, distinct variants and combinations of these genes were identified. This project aims to interrogate how variation in these critical genes impacts on the function of cytotoxic lymphocytes, providing insights into the evolutionary drivers of immune recognition mechanisms.Read moreRead less
Surface Engineered Biomaterials to Control Inflammation. The overarching aim of this project is to provide a mechanistic understanding of how surface nanotopography affects inflammatory responses. Experimental evidence demonstrates that engineered surface nanotopography in combination with surface chemistry downregulates the expression of proinflammatory cytokines from primary macrophages. The significance of these findings is that it may be possible to engineer the nanotopography of a biomedica ....Surface Engineered Biomaterials to Control Inflammation. The overarching aim of this project is to provide a mechanistic understanding of how surface nanotopography affects inflammatory responses. Experimental evidence demonstrates that engineered surface nanotopography in combination with surface chemistry downregulates the expression of proinflammatory cytokines from primary macrophages. The significance of these findings is that it may be possible to engineer the nanotopography of a biomedical device surface in a manner which leads to a desired and predictable level of inflammation and subsequent foreign body reaction (FBR) medical implants and tissue engineering constructs.Read moreRead less
Positrons in biosystems. This project aims to improve our understanding of the damage processes in Positron Emission Tomography (PET). PET is a widely used medical imaging technique, but there are gaps in our understanding of the underlying interactions, in particular in the case of the radiation damage induced during the process. By using new models incorporating accurate descriptions of interactions processes, verified by experimental measurement, this project will develop a new model of posit ....Positrons in biosystems. This project aims to improve our understanding of the damage processes in Positron Emission Tomography (PET). PET is a widely used medical imaging technique, but there are gaps in our understanding of the underlying interactions, in particular in the case of the radiation damage induced during the process. By using new models incorporating accurate descriptions of interactions processes, verified by experimental measurement, this project will develop a new model of positron transport in PET. The project will allow validation of predictions from the model by undertaking experiments in liquid water.Read moreRead less
Role of plant host factors in the replication and pathogenesis of Tomato leaf curl virus (TLCV). Geminivirus infection is an emerging problem in the Australian tomato growing industry which is currently worth ca.A$200m annually. Knowledge gained from this research will have direct benefit in safeguarding this industry by providing an insight into geminivirus replication and identifying molecular targets for virus control. More generally, the technology developed through this study will contribu ....Role of plant host factors in the replication and pathogenesis of Tomato leaf curl virus (TLCV). Geminivirus infection is an emerging problem in the Australian tomato growing industry which is currently worth ca.A$200m annually. Knowledge gained from this research will have direct benefit in safeguarding this industry by providing an insight into geminivirus replication and identifying molecular targets for virus control. More generally, the technology developed through this study will contribute to our basic understanding of virus replication in plants with a view to controlling virus diseases by direct molecular intervention with specifically engineered tools. We foresee potential industrial applications. Read moreRead less