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Use of patient mis sense mutations in SCN9A to increase our understanding of the structure and function of sodium channels

利用患者 SCN9A 错义突变来增加我们对钠通道结构和功能的理解

基本信息

批准号：
1801406
负责人：
金额：
--
依托单位：
University of Cambridge
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2016
资助国家：
英国
起止时间：
2016 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=studentship-1801406
关键词：
Use patient mis sense mutations

项目摘要

This project will explore the pathogenesis of missense mutations in the gene SCN9A encoding the protein NaV1.7. Bi-allelic non-functioning mutations in SCN9A cause Congenital Insensitivity to Pain (CIP) - where no pain is ever felt anywhere by affected individuals. The majority of CIP mutations are non-sense and thus cause no protein to be produced.However the mis-sense mutations chosen from patients for this project are far more interesting and likely to reveal novel aspects of the trafficking, channel function or essential interacting partners of NaV1.7. I will define the pathogenic mechanism of each mutation and then explore their translational potential in developing analgesic therapies. Techniques involved in this project include single cell electrophysiology, cell and molecular biology, and the use of stem cell derived nociceptors. The studentship will be supervised jointly by Professor Geoff Woods at CIMR, who leads a team investigating the genetic basis of disorders of pain sensing; and Dr John Linley at MedImmune who leads an electrophysiology team exploring novel pain signalling mechanisms. This group is part of CamPain; a collaboration between University of Cambridge Departments working together to investigate the cellular and molecular basis of pain with the aim of improving pain management and treatment.

该项目将探讨编码蛋白质 NaV1.7 的基因 SCN9A 错义突变的发病机制。 SCN9A 的双等位基因无功能突变会导致先天性疼痛不敏感 (CIP)，即受影响的个体在任何地方都感觉不到疼痛。大多数 CIP 突变是无义的，因此不会产生蛋白质。然而，从患者中为本项目选择的错义突变更有趣，并且可能揭示 NaV1.7 的运输、通道功能或重要相互作用伙伴的新方面。我将定义每个突变的致病机制，然后探索它们在开发镇痛疗法中的转化潜力。该项目涉及的技术包括单细胞电生理学、细胞和分子生物学以及干细胞衍生伤害感受器的使用。该学生奖学金将由 CIMR 的杰夫·伍兹 (Geoff Woods) 教授共同监督，他领导的团队研究疼痛感觉障碍的遗传基础； MedImmune 的 John Linley 博士领导着一个电生理学团队探索新的疼痛信号机制。该团体是 CamPain 的一部分；剑桥大学各院系之间的合作，共同研究疼痛的细胞和分子基础，旨在改善疼痛管理和治疗。