A cryo-electron microscope for structural biology, including single-particle and tomography, at KCL.

生物分子，特别是蛋白质在分子水平上的表征，对于从根本上理解生物过程以及新药开发是至关重要的。特别是，能够确定这些蛋白质如何相互作用的原子细节(蛋白质之间，而且与DNA、脂类、糖、药物等之间)，或者它们的结构在其活动过程中如何变化，对于破译它们的功能是至关重要的。近年来，电子显微镜已经成为获得此类分子信息的主要方法，2017年诺贝尔化学奖突出了这一方法学的先驱。我们寻求获得这样一台电子显微镜，这将使KCL能够获得利用这项新兴技术的能力。这台仪器将使我们不仅能够发展我们在KCL的现有研究，而且还将有助于开发新的研究途径，并用于培训下一代生物分子科学家。此外，我们寻求购买的仪器的一个核心方面是，它不仅允许在分离时获得蛋白质的分子细节，而且还可以在其生物功能的背景下观察它们。这将使我们的研究跨越尺度，从分子到细胞。特别是，我们将在我们的研究工作中广泛使用这种设备，以了解与细菌毒力和抗生素耐药性、病毒致病(包括SARS-CoV-2)、癌症和肿瘤致病以及心血管疾病有关的蛋白质。

The characterization of biomolecules, and proteins in particular, at the molecular level, is critical for the fundamental understanding of biological processes, as well as for new drug development. In particular, the capacity to determine the atomic details of how such proteins interact (between proteins, but also with DNA, lipids, sugars, drugs etc.), or how their architecture changes during their activity, is essential to decipher their function.In recent years, Electron microscopy has become the main method to obtain such molecular information, as highlighted by the 2017 Nobel prize in Chemistry to the pioneers of the methodology. We seek to acquire such an electron microscope, which will permit KCL to gain the capacity to make use of this emerging technology. This instrument will permit us to not only to develop our existing research at KCL, but will also be instrumental to develop new avenues of research, and for the training of the next generation of biomolecular scientists. In addition, a central aspect of the instrument we seek to purchase, is that it allows not only to gain molecular details of proteins in isolation, but also to observe them in the context of their biological function. This will permit us to bridge our studies across scales, from molecules to cells. In particular, we will use this equipment extensively in our research efforts to understand proteins involved in bacterial virulence and antibiotic resistance, viral pathogenesis (including SARS-CoV-2), cancer and tumour pathogenesis, and cardiovascular diseases.