权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Development of New Structural Characterisation Tools for Extracellular Matrix

细胞外基质新结构表征工具的开发

基本信息

批准号：
2110562
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：
2018
资助国家：
英国
起止时间：
2018 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=studentship-2110562
关键词：
Development New Structural Characterisation Tools

项目摘要

The project will develop new structural characterisation tools to study the molecular structure of extracellular matrix and how it is altered by non-enzymatic chemistry and cellular activity. This will include developing spectral editing tools in Dynamic Nuclear Polarisation (DNP) NMR to be able to extract NMR spectra of specific regions of the extracellular matrix from samples of intact, ex vivo matrix. For instance, we will utilise the fact that key cell adhesion proteins contact the extracellular matrix through metal-mediated binding, where the native metal ion can be replaced by a paramagnetic ion, e.g. Ca2+ can be replaced by Co2+ in integrin binding sites. Paramagnetic ions will quench the DNP effect in their locality, resulting in a DNP NMR spectrum in which NMR signals from the integrin binding site are absent. Subtraction of this paramagnetic-edited spectrum from one collected on the sample containing diamagnetic metal ions instead of paramagnetic gives an NMR spectrum of the integrin binding sites. In a second part of the project we will develop methods to measure NMR spectra on extracellular matrix whilst the matrix is under mechanical stress, with the aim of following changes in molecular conformation during that process.Overall, her project will deliver new tools to enable novel insight into biological processes highly relevant to ageing and degenerative diseases.

该项目将开发新的结构表征工具，以研究细胞外基质的分子结构以及非酶化学和细胞活动如何改变它。这将包括开发动态核极化(DNP)核磁共振的光谱编辑工具，以便能够从完整的体外基质样本中提取细胞外基质特定区域的核磁共振光谱。例如，我们将利用这样一个事实，即关键的细胞黏附蛋白通过金属介导的结合与细胞外基质接触，其中天然金属离子可以被顺磁性离子取代，例如整合素结合部位的钙离子可以被Co2+取代。顺磁离子将在其局域内猝灭DNP效应，导致DNP核磁共振谱中没有来自整合素结合部位的核磁共振信号。从含有抗磁性金属离子而不是顺磁性的样品上收集的光谱减去顺磁编辑的光谱，得到整合素结合位置的核磁共振光谱。在项目的第二部分，我们将开发测量细胞外基质在机械应力下的核磁共振光谱的方法，目的是跟踪这一过程中分子构象的变化。总体而言，她的项目将提供新的工具，使人们能够对与衰老和退行性疾病高度相关的生物过程进行新的洞察。