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

蛋白质构象、蛋白质错误折叠、hIAPP、离子淌度质谱

• 批准号: 2869746
• 金额: --
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2869746
• 关键词: Protein; conformation; misfolding; hIAPP; Ion

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.

该学生将在罗利实验室（Raleigh Lab）中的淀粉样蛋白生成多肽以及在Thalassinos实验室中使用IMMS和Python编程的固体肽合成，纯化和生物物理表征。与所有最先进的技术一样，分析CIMM和ECD数据的软件并不那么先进，因此教学学生Python将使他们能够为处理数据的更有效的方法来设置更有效的方法。对水域的访问将为CIMMS提供进一步的培训，以设计和优化ECD脆弱性，但在当前在Waters in wilslow specection中的其他最先进的技术中，还可以在其他最先进的技术中进行培训。 Wilmslow的研究实验室目前是英国唯一具有收费检测质谱原型的实验室。我们将首先使用我们的跨学科方法来研究野生型HIAAP，此后，我们将重点介绍杂合S20G突变，在亚洲人的个体中发现，并与糖尿病的风险增加有关。 S20G突变体形成淀粉样蛋白的淀粉样蛋白比WildType Hiapp在体外更快，并导致培养的胰岛中广泛的淀粉样蛋白形成并增加毒性。增强聚集的原因尚不清楚，突变的毒性作用的起源也不是。