Protein conformation, Protein misfolding, hIAPP, Ion mobility mass spectrometry

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The student will be trained in solid peptide synthesis, purification, and biophysical characterisation of amyloidogenic polypeptides in the Raleigh lab and in the use of IMMS and Python programming in the Thalassinos lab. As with all cutting-edge technology, the software to analyse cIMMS and ECD data is not as advanced so teaching the student Python will allow them to device more efficient ways of processing their data.Visits to Waters will provide further training in the use of the cIMMS devise and optimisation of the ECD fragmentation but also in additional cutting-edge technology currently under development at Waters in Wilmslow, particularly charge detection mass spectrometry. The research lab at Wilmslow is currently the only lab in the UK to have a charge detection mass spectrometry prototype.We will begin by using our interdisciplinary approach to study the wild type hIAAP, after which we will focus on the heterozygous S20G mutation, found in individuals of Asian origin and which is linked to an increased risk of diabetes. The S20G mutant forms amyloid more rapidly than wildtype hIAPP in vitro and leads to extensive amyloid formation in cultured islets and heighted toxicity. The reasons for the enhanced aggregation are not understood nor are the origins of the toxic effects of the mutation.