Collaborative Computational Project for Electron cryo-Microscopy (CCP-EM): Supporting the software infrastructure for cryoEM techniques.

了解生物分子如何在细胞内发挥作用，对于抗击疾病至关重要。虽然多年来，大分子结晶学和核磁共振光谱等实验技术一直提供了关于细胞中重要分子的详细信息，但现在人们的注意力转移到这些分子如何相互作用以及它们在细胞中的位置如何影响上。电子冷冻显微镜(Cryo-EM)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一座桥梁。在最有利的情况下，可以获得分子组装的详细图像，而在较低分辨率的电子断层图像可以显示细胞或组织完整部分的内部分子细节。近年来，由于仪器和数据处理技术的进步，低温电子显微镜的应用有了显著的提高，使其成为结构和细胞生物学中最重要的实验技术之一。要完全开发低温EM，需要好的软件来处理原始实验数据，并从分子或细胞结构的角度对其进行解释。然而，软件的提供是零散和零散的，个别实验室在试图为其项目创建合适的软件环境时面临着陡峭的学习曲线。大分子结晶界在30多年前就面临着这样的挑战，而协作计算第四号项目(CCP4)就是为了应对这一挑战而创建的。在接下来的几年里，CCP4已经成长为一个重要的国际项目，并在分子水平上支持了我们对细胞理解的许多进展。在过去的10年里，已经创建了类似的结构生物学合作项目：用于核磁共振光谱的CCPN，用于生物分子模拟的CCPBioSim，以及用于小角X射线和中子散射的CCP-SAS。为了应对低温EM日益增长的科学作用，我们最近创建了电子冷冻显微镜协同计算项目(CCP-EM)。英国至少有25个小组活跃在低温EM领域，寻求从低温EM获得补充信息的晶体小组数量迅速增加。CCP-EM向所有这些团体开放，并将协调英国社区内的努力。它将通过传播有关现有软件、服务台支持和定向培训的信息来支持用户。它将通过技术帮助和帮助向社区分发他们的软件来支持开发人员。CCP-EM还在开发自己的软件套件，通过将现有程序整合到一个强大和用户友好的框架中来处理低温EM数据。CCP-EM的创建是通过授予伙伴关系赠款来促进的，我们现在寻求后续的伙伴关系赠款，以支持合作项目的成熟和扩展。虽然第一笔拨款集中在单粒子技术上，其中单个分子或络合物被成像，但我们现在建议将范围扩大到电子断层扫描，它提供对细胞中的络合物和更大结构的原位成像。CCP-EM的继续将导致更好地在UK组内使用软件。一群敬业的科学家的支持将大大加快建立新团队或帮助老牌显微镜专家进入新领域(如断层摄影术)的进程。CCP-EM将直接支持位于哈维尔校区的新的国家EM设施，帮助用户最大限度地利用新资源。然而，最重要的成果是发展了一种社区精神，这种精神鼓励个人科学家共同努力。在英国创建科学社区将使公共资金得到最佳利用，并使英国在显微镜设施上的投资获得最大回报

Understanding how biological molecules function inside cells is vital to combating disease. While experimental techniques such as macromolecular crystallography and nuclear magnetic resonance spectroscopy have for many years given detailed information on important molecules in the cell, attention is now moving to how these molecules interact with each other and how they are affected by their location in the cell. Electron cryo-Microscopy (cryo-EM) 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 have led to a significant increase in the application of cryo-EM in recent years, such that it is now one of the most important experimental techniques available in structural and cellular biology. To exploit fully cryo-EM requires good software for processing the primary experimental data and for interpretating it in terms of molecular or cellular structure. However, software provision is patchy and fragmented, and individual labs face a steep learning curve when trying to create a suitable software environment for their projects. The macromolecular crystallography community faced such a challenge more than 30 years ago, and the Collaborative Computational Project No. 4 (CCP4) was created to address this challenge. In the years following, CCP4 has grown to be a major international project, and has underpinned many of the advances in our understanding of cells at the molecular level. In the last 10 years, similar collaborative projects for structural biology have been created: CCPN for nuclear magnetic resonance spectroscopy, CCPBioSim for biomolecular simulation, and CCP-SAS for small angle X-ray and neutron scattering. In response to the growing scientific role of cryoEM, we have recently created the Collaborative Computational Project for Electron cryo-Microscopy (CCP-EM).There are at least 25 groups in the UK active in the field of cryo-EM, with a rapidly increasing number of crystallography groups looking to obtain complementary information from cryoEM. CCP-EM is open to all these groups, and will coordinate efforts within the UK community. It will support users through dissemination of information on available software, helpdesk support, and directed training. It will support developers through technical help and by helping to distribute their software to the community. CCP-EM is also developing its own software suite for processing cryoEM data by integrating existing programmes into a robust and user-friendly framework. The creation of CCP-EM was facilitated by the award of a Partnership Grant, and we now seek a follow-on Partnership Grant to support the collaborative project as it matures and expands. While the first grant focussed on single particle techniques, wherein individual molecules or complexes are imaged, we now proposed to expand the scope to electron tomography which provides in situ imaging of complexes and larger structures in the cell.A continuation of CCP-EM will lead to a better use of software within UK groups. The support of a dedicated group of scientists will greatly speed up the process of establishing new groups or helping established microscopists move into new areas (such as tomography). CCP-EM will directly support the new national EM facility on the Harwell Campus, helping users get the most from a new resource. However, the most important output is the development of a community spirit, that encourages individual scientists to pool their efforts. The creation of scientific communities in the UK leads to the best use of public money, and maximises the return on the UK's investment in microscopy facilities