Super-resolution Cryo-Correlative Light and Electron Microscopy to studying macromolecular structure in the cell nanocontext

超分辨率冷冻相关光和电子显微镜研究细胞纳米背景中的大分子结构

• 批准号: 1982026
• 金额: --
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1982026
• 关键词: Super; resolution; Cryo; Correlative; Light

To understand complex biological structure and function, we need more comprehensive imaging strategies. Cryo-correlative light and electron microscopy (cryo-CLEM) has been put into the frontline of bio-imaging method and development. Cryo-electron microscopy (cryo-EM) is a powerful tool to obtain up to sub-nanometre resolution molecular and cellular ultrastructure. Cryo-fluorescence microscopy (cryo-FM) takes the leading role to study the distribution and organisation of specific biomolecules in cells. Cryo-CLEM is a powerful way to link function to structure in complex biological systems; however a major drawback is the discrepancy in resolving power between cryo-EM (nanometre scale) and cryo-FM (a few hundred number scale). We propose to develop super-resolution cryo-FM, leading to the development of a new imaging method offering macromolecular level optical resolution on bio-samples preserved in a near-native state. The development will pave the way for the deployment of highly demanded super-resolution cryo-CLEM, enabling a variety of correlative biological structure and function studies.

为了了解复杂的生物结构和功能，我们需要更全面的成像策略。低温相关光电子显微镜（cryo-CLEM）已成为生物成像方法和发展的前沿。低温电子显微镜（cryo-EM）是获得亚纳米分辨率分子和细胞超微结构的有力工具。低温荧光显微镜（cryo-FM）是研究细胞中特定生物分子分布和组织的主要手段。Cryo-CLEM是将复杂生物系统的功能与结构联系起来的有力方法；然而，低温电镜（纳米尺度）和低温调频（几百数尺度）的主要缺点是分辨能力的差异。我们建议开发超分辨率冷冻调频，从而开发一种新的成像方法，为保存在接近天然状态的生物样品提供大分子水平的光学分辨率。这一发展将为高需求的超分辨率低温clem的应用铺平道路，使各种相关的生物结构和功能研究成为可能。