A next-generation computing platform for electron microscopy at Imperial College

在细胞中，蛋白质就像执行复杂生物功能的微小分子机器。许多蛋白质在大型组装中协同工作，这很难研究，因为它们是动态的。为了看到蛋白质复合体的作用，我们使用了一种名为低温电子显微镜的方法，在这种方法中，我们拍摄了数十万张蛋白质快照，并用计算机将这些图像组合在一起，创建了一个三维模型。使用这些模型，我们可以了解蛋白质如何与结合伙伴相互作用，在细胞内完成他们的工作。计算是从电子显微镜图像生成结构模型的重要部分。此前，研究人员在办公桌前使用个人电脑处理数据。这不再可能，因为这些计算中使用了大量的图像和涉及的计算机程序的复杂性。计算机游戏行业推动了图形计算技术的进步，我们使用图形计算来处理蛋白质的图像。这项提议是为了在伦敦帝国理工学院建立一个将高性能文件存储系统与图形计算资源相结合的计算平台，以处理低温电子显微镜数据。这个计算平台将允许我们更快地解决更多的结构，并使研究人员能够更快地使用这些数据来通知新的实验。这项提议将支持帝国理工学院致力于理解生命规则的结构生物学研究。许多直接受益于这种计算设备的项目正在应对BBSRC在可持续农业、对健康的综合理解和数据驱动生物学方面的战略挑战。这项提案中有一半的合作伙伴正在研究抗菌素耐药性机制背后的基本生物学过程。利用这一计算平台生成的新结构模型将为发现改善人类健康的疗法奠定基础。

In a cell, proteins are like tiny molecular machines carrying out complex biological functions. Many proteins work together in large assemblies that are difficult to study because they are dynamic. To see protein complexes in action, we use a method called cryo electron microscopy in which we take hundreds of thousands of protein snapshots, and with a computer, combine these images to create a three-dimensional model. Using these models, we can understand how proteins interact with binding partners to do their jobs inside cells. Computing is an important part of generating structural models from electron microscopy pictures. Previously, researchers used individual computers at their desks to process data. This is no longer possible because of the large number of images used in these calculations and the complexity of the computer programmes involved. The computer gaming industry has driven technology advances in graphical computing which we use to process images of proteins. This proposal is for a computing platform that combines a high-performance file storage system with graphical computing resources to process cryo electron microscopy data at Imperial College London. This computing platform will allow us to solve more structures quicker and enable researchers use these data to inform new experiments faster. This proposal will support structural biology research at Imperial that works toward understanding the rules of life. Many of the projects that directly benefit from this computing equipment are tackling BBSRC strategic challenges in sustainable agriculture, an integrated understanding of health, and data-driven biology. Half of the CoIs on this proposal are researching the fundamental biological processes underlying antimicrobial resistance mechanisms. Together new structural models generated using this computing platform will lay the foundation for the discovery of therapeutics to improve human health.