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

学生将在罗利实验室接受固体肽合成，纯化和淀粉样蛋白生成多肽的生物物理特性的培训，并在Thalassinos实验室使用IMMS和Python编程。与所有尖端技术一样，分析cIMMS和ECD数据的软件并不先进，因此教授学生Python将使他们能够设计更有效的数据处理方法。参观沃茨将提供关于cIMMS设计和ECD碎片优化的进一步培训，以及目前在威姆斯洛沃茨开发的其他尖端技术，特别是电荷检测质谱法。Wilmslow的研究实验室是目前英国唯一拥有电荷检测质谱原型的实验室。我们将开始使用我们的跨学科方法研究野生型hIAAP，之后我们将专注于杂合S20 G突变，在亚洲血统的个体中发现，这与糖尿病风险增加有关。S20G突变体在体外比野生型hIAPP更快地形成淀粉样蛋白，并导致培养的胰岛中广泛的淀粉样蛋白形成和毒性增加。增强聚集的原因尚不清楚，突变毒性作用的起源也不清楚。

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.