Development of solid-state NMR spectroscopic approaches for investigation of biological extracellular matrices

固态核磁共振（ssNMR）是一种多功能的技术，可以提供生物分子在功能相关状态下的结构信息。然而，ssNMR在被称为细胞外基质（ECM）的生物材料中的应用仍然有限。ecm具有多样性，通常由分子实体的异质混合物组成，包括蛋白质、聚糖、糖蛋白和其他生物分子。这些分子在一定长度范围内表现出特定的相互作用和组织。SsNMR可以在原子长度尺度上提供结构洞察，可能用于体外样品（例如来自细胞培养）和离体样品（例如来自患者活检），只需最少的处理或纯化。本项目的目的是开发一种通用的方法来研究不同来源生物的ecm使用ssNMR光谱。具体目标包括：开发方法，将ssNMR与快速MAS （60 kHz+）和高磁场相结合，为ecm带来新的见解。含有层粘连蛋白的凝胶/涂层的研究，层粘连蛋白是一种用于支持干细胞体外生长的关键糖蛋白。该项目将建立在现有的生物ssNMR技术的基础上，以实现新的应用，符合EPSRC职权范围内的以下主题和关键兴趣：分析科学、生物物理学、医疗保健技术、抗菌素耐药性（真菌）生物材料。该项目的合作者包括华威医学院的Darius Koester博士和Mohan Balasubramanian教授。

Solid-state nuclear magnetic resonance (ssNMR) is a versatile technique that can provide structural information on biomolecules in functionally-relevant states. However, applications of ssNMR to biological materials known as the extracellular matrix (ECM) remain limited. There is a diversity of ECMs, which are usually composed of a heterogeneous mixture of molecular entities, including proteins, glycans, glycoproteins, and other biomolecules. These molecules show specific interactions and organisation at a range of length scales. SsNMR can contribute structural insight at the atomic length scale, potentially on in vitro samples (e.g. from cell culture) and ex vivo samples (e.g. from patient biopsies) with minimal processing or purification.The aim of this project is to develop a general approach for investigating ECMs of different source organisms using ssNMR spectroscopy. Specific objectives include:Developing methods to bring new insight to ECMs using ssNMR combined with fast MAS (60 kHz+) and high magnetic fields.Investigation of gels/coatings containing laminin, a key glycoprotein used for supporting stem cell growth in vitroInvestigation of ECM from mammalian fibroblasts from patients with Ehlers-Danlos syndromes.Investigation of cell wall from the fungi Schizosaccharomyces pombeThis project will build on existing techniques in biological ssNMR for novel applications, matching the following topics and key interests within the remit of EPSRC:Analytical scienceBiophysicsHealthcare technologiesAntimicrobial resistance (fungal)BiomaterialsCollaborators for this project include Dr Darius Koester and Prof Mohan Balasubramanian of the Warwick Medical School.