Re-designing Antibodies for Cellular imaging and Early Cancer Diagnosis We have been developing a new class of antibodies/affibodies that form covalent bonds to endogenous protein targets. Even high affinity antibodies generally dissociate from their targets on the time-scale of minutes. Antibodies that do not dissociate from their targets should reduce the detection limit of tumour markers, to allow earlier cancer diagnosis. We are applying this work to understand the role of growth factor receptor signalling in cell survival and to enable new possibilities for isolation of circulating tumour cells (CTCs).                                A New Generation of Protein Interactions The interaction of streptavidin with biotin is one of the strongest non-covalent interactions in nature. Streptavidin is widely used in biological research and also has shown success in clinical trials. We were able to make a version of streptavidin with 10-fold slower biotin dissociation. We have been investigating the increased mechanical strength of this interaction by single-molecule force spectroscopy with Vincent Moy in Miami and by crash-testing using bacterial DNA pumps with David Sherratt in this department. We are also exploring the structural basis for the extreme stability.          Peptide tags are central to protein analysis and isolation, but they are also “slippery”- it is hard to get a strong grip on them. We have harnessed and adapted an amazing feature of the hairs (pili) on the pathogenic bacterium Streptococcus pyogenes. This enabled us to achieve an irreversible covalent bond between genetically-encoded protein and peptide partners; this bond is stable over time, at high temperatures, and against the forces in biological systems (blood flow, cell migration, molecular motors). We are extending the scope of this reaction, to create new protein architectures for synthetic biology. Nanoparticles to Analyse Receptor Dynamics at the Single Molecule Level Most biological experiments observe the behaviour of hundreds to millions of molecules. Being able to study molecules in the cell one at a time can give dramatic new insights into the cell's function. We have developed new ways to target quantum dots (QDs), ultra-bright nanoparticles, to study cell surface receptors. In particular we have used QDs to understand the LDL receptor, which has a central role in preventing heart disease and may also be important in the capture of lipid-soluble antigens to activate the anti-tumour immune response. Get in contact for further information about any of these projects, or to discuss the possibility of working on other projects in the area of bionanotechnology / cancer biology.
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