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Collaborative Computational Project for Electron cryo-Microscopy (CCP-EM): 2021 - 2026

电子冷冻显微镜协作计算项目 (CCP-EM)：2021 - 2026

基本信息

批准号：
MR/V000403/1
负责人：
Martyn Winn
金额：
$ 208.4万
依托单位：
Science and Technology Facilities Council
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2021
资助国家：
英国
起止时间：
2021 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=MR%2FV000403%2F1
关键词：
Collaborative Computational Project Electron cryo

项目摘要

The behaviour of living systems ultimately comes down to the interactions of biological molecules inside cells, and understanding these is vital to numerous human efforts, including controlling disease and improving food production. While experimental techniques such as macromolecular crystallography have for many years given detailed information on important molecules in the cell, many classes of molecules are not amenable to this technique. Moreover, as our understanding of pathways in the cell grows, there is increasing interest in the context in which these molecules operate. In other words, where in the cell do these molecules do their job, and which other cellular components are necessary for their function. Electron cryo-Microscopy (cryoEM) provides very useful information here, and bridges the gap between individual molecules and the whole cell. In the most favourable cases, detailed images of assemblies of molecules can be obtained, while at lower resolutions electron tomograms can show internal molecular details from within intact parts of cells or tissues. Advances in instrumentation and data processing led to a significant increase in the quality of cryoEM data, which was characterised in 2014 as the "Resolution Revolution", and recognised by the 2017 Nobel Prize in Chemistry. Consequently there has been a surge in interest in the technique from structural and cellular biologists trying to understand a wide range of biological systems. There has been significant investment in the research infrastructure supporting cryoEM, most notably the establishment of several electron microscope facilities around the country. In the last few years, pharmaceutical companies and biotechnology companies have recognised the importance of cryoEM to their discovery pipelines, and have also begun investing in the area. A key component of this research infrastructure is the computational support to manage the data, process the micrographs, and interpret the data in terms of molecular volumes and/or atomic structures. The Collaborative Computational Project for Electron cryo-Microscopy (CCP-EM) was established during the period 2012 - 2016 to provide this part of the research infrastructure.The proposed project is intended to provide continued support to the cryoEM community. One of the major products of the CCP-EM partnership is a software suite for processing cryoEM data collected at microscope facilities. Individual computer programs in this suite are developed independently, either by members of CCP-EM or collaborators. The role of CCP-EM is to collate these programs into a single suite, develop workflows through the suite, and distribute the suite to practising scientists. When done well, this is a win-win arrangement in which scientists get access to a comprehensive set of software in one place, and methods developers get access to a large user base. It is well known, however, that software rapidly becomes unusable if not actively maintained and it is the responsibility of the core team of CCP-EM to ensure the longevity of software in the suite.We will also expand the scope of the suite. We will improve the tools for validating the structural information obtained, and facilitate the deposition of data in international archives. We will help to drive FAIR principles - that data from cryoEM experiments are accessible and usable to the wider community. We will increase our support for sub-tomogram averaging, a particular technique for obtaining in situ structural information of molecules. Finally, we will make more use of machine learning i.e. advanced algorithms that can learn from the data.All these advances will be tightly coupled with our on-going user training programme, and support for individual methods developers. We will also continue our very popular annual Spring Symposium, which now provides a forum for 300 researchers to share experiences and to develop the cryoEM community.

生命系统的行为最终归结为细胞内生物分子的相互作用，了解这些对人类的许多努力至关重要，包括控制疾病和提高粮食产量。虽然大分子晶体学等实验技术多年来已经提供了细胞中重要分子的详细信息，但许多种类的分子并不适用于这种技术。此外，随着我们对细胞通路的理解不断加深，人们对这些分子运作的环境越来越感兴趣。换句话说，这些分子在细胞的什么地方发挥作用，哪些其他细胞成分是它们发挥作用所必需的。电子冷冻显微镜（cryoEM）在这里提供了非常有用的信息，并在单个分子和整个细胞之间架起了桥梁。在最有利的情况下，可以获得分子集合的详细图像，而在较低分辨率下，电子断层扫描可以显示细胞或组织完整部分的内部分子细节。仪器和数据处理的进步导致低温低温数据质量的显着提高，这在2014年被描述为“分辨率革命”，并获得2017年诺贝尔化学奖的认可。因此，结构和细胞生物学家对这项技术的兴趣激增，他们试图了解广泛的生物系统。在支持冷冻电镜的研究基础设施方面已经有了重大投资，最值得注意的是在全国各地建立了几个电子显微镜设施。在过去的几年里，制药公司和生物技术公司已经认识到低温冷冻技术对他们的发现管道的重要性，并且也开始在该领域进行投资。该研究基础设施的一个关键组成部分是管理数据的计算支持，处理显微照片，并根据分子体积和/或原子结构解释数据。电子冷冻显微镜（CCP-EM）协作计算项目于2012年至2016年期间建立，以提供这部分研究基础设施。拟议的项目旨在为cryoEM社区提供持续的支持。CCP-EM合作伙伴关系的主要产品之一是用于处理显微镜设备收集的冷冻电镜数据的软件套件。该套件中的单个计算机程序由CCP-EM成员或合作者独立开发。CCP-EM的作用是将这些程序整理成一个单独的套件，通过套件开发工作流程，并将套件分发给实践科学家。如果做得好，这是一个双赢的安排，科学家可以在一个地方访问一套全面的软件，而方法开发人员可以访问一个庞大的用户群。然而，众所周知，如果不积极维护，软件很快就会变得不可用，并且CCP-EM的核心团队有责任确保套件中软件的寿命。我们还将扩大套房的范围。我们将改进验证所获得的结构信息的工具，并促进数据在国际档案中的存放。我们将帮助推动FAIR原则，即更广泛的社区可以访问和使用低温低温实验数据。我们将增加对亚层析图平均的支持，这是一种获得分子原位结构信息的特殊技术。最后，我们将更多地利用机器学习，即可以从数据中学习的高级算法。所有这些进步将与我们正在进行的用户培训计划以及对个别方法开发人员的支持紧密结合在一起。我们还将继续举办非常受欢迎的年度春季研讨会，现在为300名研究人员提供了一个分享经验和发展低温em社区的论坛。