Accelerating throughput at Scotland's national Cryo-EM centre - a next generation direct electron detector for SCMI.

结构生物学家努力在原子水平上理解生物分子的形状，即“生命机器”。1953年，沃森和克里克发表了最著名的生物分子结构--DNA。在我们的每个细胞中，我们的整个基因组，告诉我们的身体如何制造和维持我们的信息，都写在这个优雅的双螺旋结构中，使用只有四个字母的字母表。我们的细胞对我们基因组的解释导致了大量蛋白质分子的产生。这些是更复杂的结构，是我们的DNA是蓝图的机器。要了解生物过程，例如病毒如何进入我们的身体并引起疾病，需要我们努力了解蛋白质分子的形状。以病毒为例，比如在过去几年里引起大流行并极大地改变了我们生活的冠状病毒，我们希望了解病毒蛋白质的结构，以及它们如何与我们自身的蛋白质相互作用而导致疾病。为此，我们纯化蛋白质，冷冻它们，并在非常强大的显微镜下成像。这个过程被称为低温电子显微镜，或更常见的“cryo-EM”。来自冷冻EM的图像可以在计算机中处理，以高分辨率计算感兴趣的蛋白质分子的形状。在MRC -格拉斯哥大学病毒研究中心（CVR），我们使用位于我们大楼内的苏格兰高分子成像中心（SCMI）的设备进行冷冻电镜实验。该中心成立于2018年，是英国为数不多的高性能冷冻EM中心之一，也是苏格兰唯一的一个。我们希望通过增加最先进的相机系统，建立SCMI更快地解决蛋白质结构和更高分辨率的能力。这将大大加快我们的实验速度，使研究人员能够在4到5个小时内收集足够的cryo-EM图像来解决他们的蛋白质结构，而不是目前需要的2到3天。Cryo-EM设备运行非常昂贵-一天的显微镜时间花费超过1000英镑。这项投资将大大提高我们的科学效率和我们能够解决的结构质量。

Structural biologists strive to understand the shape of biological molecules, the 'machinery of life', at the atomic level. In 1953, Watson and Crick published the most famous structure of a biological molecule - that of DNA. In each of our cells, our entire genome, the information that tells our bodies how to make and maintain us, is written in to this elegant double-helix structure, using an alphabet of only four letters. The interpretation of our genome, by our cells, leads to the production of a vast array of protein molecules. These are much more complex structures, and are the machines for which our DNA is the blue-print. To understand biological processes, such as how a virus can enter our bodies and cause disease, requires us to work to understand the shapes of protein molecules. In the case of a virus, such as the coronavirus that caused a pandemic and changed our lives so dramatically these past few years, we wish to understand the structures of the proteins that the virus is made of, and how they interact with our own proteins to cause disease.To do this, we purify the proteins, freeze them, and image them in a very powerful microscope. This process is called cryogenic electron microscopy, or more commonly 'cryo-EM'. Images from cryo-EM can be processed in computers, to calculate the shapes of the protein molecule of interest at high resolution. This allow us to build a model of the protein in which we can confidently define the position of individual atoms.In the MRC - University of Glasgow Centre for Virus Research (CVR), we perform cryo-EM experiments using the facilities available at the Scottish Centre for Macromolecular Imaging (SCMI), which is located in our building. This centre was established in 2018 and is one of only a handful of high-performance cryo-EM centres in the United Kingdom, and the only one in Scotland. We wish to build the capacity of the SCMI to solve protein structures faster, and to higher resolution, by the addition of a state-of-the-art camera system. This will dramatically speed up our experiments, allowing researchers to collect enough cryo-EM images to solve their protein structures in four to five hours, rather than the two to three days currently required. Cryo-EM equipment is very expensive to run - one day of microscope time costs more than £1,000. This investment will greatly improve the efficiency of our science and the quality of structures we are able to solve.