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.
Can technology make communication in complex systems safer and more efficient? Evaluation of an electronic test management system in health care. In many industries poor communication has a major impact on safety; in health, missed test results have impacts ranging from inappropriate antibiotic therapy to missed cancer diagnoses. This research will evaluate new information technology which can improve health outcomes and communication between clinicians, laboratories and patients.
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
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
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
Biological and behavioural rhythms of Delayed Sleep Phase Disorder. Delayed Sleep Phase Disorder is a disabling and prevalent sleep disorder in the adolescent and young adult population. Using an innovative laboratory method this project will carry out the world's first comprehensive study of it. The results of this study will point the way to an effective treatment of this presently poorly treated disorder.
Development of Pyrrolopyrimidines as Inhibitors of ATP-Binding Proteins. This project seeks to generate analogues of natural products that have been found to be active against cancer cells and tropical parasites. The new materials produced by this project will aid in the study of biochemical processes involved in diseases such as cancer and lymphatic filariasis, thus leading the way to development of these compounds as potential treatments for such diseases.
Gas Phase Reactivity of Charged Peptide and DNA Radicals: Fundamentals and Applications. Radicals derived from the "molecules of life", proteins and DNA, play both beneficial (e.g. enzyme catalysis) and deleterious roles (e.g. protein and DNA damage associated with disease). Two electrospray ionisation mass spectrometry approaches have been discovered to generate charged radicals of related models systems (e.g. peptides and nucleobases). The gas phase chemistry of these species is a largely unch ....Gas Phase Reactivity of Charged Peptide and DNA Radicals: Fundamentals and Applications. Radicals derived from the "molecules of life", proteins and DNA, play both beneficial (e.g. enzyme catalysis) and deleterious roles (e.g. protein and DNA damage associated with disease). Two electrospray ionisation mass spectrometry approaches have been discovered to generate charged radicals of related models systems (e.g. peptides and nucleobases). The gas phase chemistry of these species is a largely unchartered area! We will examine the fundamental chemistry (unimolecular and bimolecular reactions) of these systems and build upon some exciting preliminary results which suggest potential applications (e.g. as a proteomics tool to sequence and distinguish between leucine and isoleucine residues in peptides).Read moreRead less
Plasma-soft tissue interactions: advancing a new era of plasma technologies. This project aims to develop the prerequisite knowledge to underpin new plasma technologies. Specifically, the project plans to provide new insight into the interaction between ionised gas plasma jets and biological soft tissue. It plans to use advanced analytical techniques and modelling simulations to investigate the physics of the plasma jet and processes occurring at the jet–tissue interface. It also plans to use (b ....Plasma-soft tissue interactions: advancing a new era of plasma technologies. This project aims to develop the prerequisite knowledge to underpin new plasma technologies. Specifically, the project plans to provide new insight into the interaction between ionised gas plasma jets and biological soft tissue. It plans to use advanced analytical techniques and modelling simulations to investigate the physics of the plasma jet and processes occurring at the jet–tissue interface. It also plans to use (bio)engineered tissue targets, chemical, biological and cellular assays to probe the transport and effects of plasma reactive species deep within tissue. This new knowledge would enable the development of new plasma sources and protocols for applications in health, medicine, biotechnology and manufacturing.Read moreRead less