Cryo-electron microscope for structural and cell biology

与传统的电子显微镜(EM)不同，低温EM样品既不脱水也不染色，因此样品的结构保持接近自然环境中水合结构的形状。大分子和亚细胞结构被证明是冷冻EM的极好靶点。我们正在申请购买低温电子显微镜(Cryo-EM)的资金，以改变我们在结构分子生物学和细胞生物学研究方面的影响。最近的进展，包括直接电子探测器和修正电子束中分子运动的数据处理，已经使冷冻电子显微镜发生了革命性的变化，使确定大分子和纳米机器的原子分辨结构成为可能。这一结果将对伦敦玛丽女王大学的结构生物学和细胞生物学研究产生革命性的影响。这项建议是特别及时的，因为我们最近聘请了结构生物学家，他们需要使用低温EM(Darbari，Garnett，Milanesi)，刚刚获得了泰坦Krios的高分辨率数据收集(Pickersgill co-I)，我们有一些活跃的和正在开发的项目，通过生命周期，对抗抗菌素耐药性，合成生物学和生物能源，冷冻-EM将提供一个步骤改变对系统生物学的理解。我们也有几名现有的工作人员需要访问冷冻EM，包括单颗粒分析和冷冻断层扫描，以允许进行超微结构成像。最后，我们在2017/18年度还将在这些领域进行四项任命。这些设备还将改变我们培训下一代研究人员的能力，包括我们的本科生(MSCI)和博士生，包括来自BBSRC Lido DTP的学生。

Unlike conventional electron microscopy (EM), cryo-EM samples are neither dehydrated nor stained and so the structure of samples remain close to the shape for the hydrated structure in the native environment. Large macromolecules and subcellular structures are proving to be excellent targets for cryo-EM. We are applying for funds for the acquisition of a cryo-electron microscope (cryo-EM) to transform the impact of our research in structural molecular biology and cell biology. Recent advances, which include direct electron detectors and data processing to correct for molecular movement in the electron beam, have revolutionised cryo-electron microscopy making it possible to determine atomic resolution structures of macromolecules and nano-machines. The results will be transformative for research in structural biology and cell biology at Queen Mary University of London. This proposal is especially timely as we have recently employed structural biologists who need access to cryo-EM (Darbari, Garnett, Milanesi), just secured access to a Titan Krios for high-resolution data collection (Pickersgill co-I), and we have a number of active and of developing projects in healthy ageing through the lifecourse, combating antimicrobial resistance, synthetic biology and bioenergy for which cryo-EM will provide a step-change in understanding the biology of the systems. We also have several existing staff who need to access cryo-EM, both single particle analysis and cryo-tomography to allow ultrastructural imaging. Finally, we have four further appointments to make in these areas in 2017/18. The equipment will also transform our ability to train the next generation of researchers, both our undergraduate students (MSci) and PhD students including those from the BBSRC LIDO DTP.