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对抗疾病至关重要。虽然大分子晶体学和核磁共振波谱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，但现在人们的注意力正在转向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它们。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。近年来，仪器和数据处理的进步导致低温电镜的应用显著增加，因此它现在是结构和细胞生物学中最重要的实验技术之一。为了充分利用低温电镜技术，需要良好的软件来处理原始实验数据，并根据分子或细胞结构对其进行解释。然而，软件供应是零零碎碎的，当试图为他们的项目创建合适的软件环境时，单个实验室面临着陡峭的学习曲线。大分子晶体学界在30多年前就面临着这样的挑战，而协作计算项目4 （CCP4）的创建就是为了应对这一挑战。在接下来的几年里，CCP4已经发展成为一个重要的国际项目，并为我们在分子水平上对细胞的理解奠定了许多基础。在过去的10年里，类似的结构生物学合作项目已经创建：CCPN用于核磁共振波谱，CCPBioSim用于生物分子模拟，CCP-SAS用于小角度x射线和中子散射。为了响应冷冻电镜日益增长的科学作用，我们最近创建了电子冷冻显微镜（CCP-EM）的协作计算项目。在英国至少有25个小组活跃在低温电镜领域，随着晶体学小组的数量迅速增加，他们希望从低温电镜中获得补充信息。CCP-EM向所有这些团体开放，并将协调英国社区内的努力。它将通过传播有关可用软件的信息、帮助台支持和指导培训来支持用户。它将通过技术帮助和帮助向社区分发软件来支持开发人员。CCP-EM还在开发自己的软件套件，通过将现有程序集成到一个强大且用户友好的框架中来处理低温低温数据。CCP-EM的创建得益于伙伴关系补助金的奖励，我们现在正在寻求后续伙伴关系补助金，以支持该合作项目的成熟和扩展。虽然第一笔拨款侧重于单粒子技术，其中单个分子或复合物成像，但我们现在提议将范围扩展到电子断层扫描，以提供细胞中复合物和更大结构的原位成像。CCP-EM的延续将导致英国企业更好地使用软件。一个专门的科学家小组的支持将大大加快建立新小组的进程，或帮助已有的显微镜专家进入新的领域（如断层扫描）。CCP-EM将直接支持Harwell校区新的国家EM设施，帮助用户从新资源中获得最大收益。然而，最重要的成果是培养了一种鼓励科学家个体共同努力的社区精神。在英国，科学团体的建立导致了公共资金的最佳利用，并使英国在显微镜设备上的投资回报最大化

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