MRI: Acquisition of Cryo-EM for Southwest Regional Center

MRI：为西南区域中心采购冷冻电镜

• 批准号: 1531991
• 负责人: John Spence
• 金额: $ 282.55万
• 依托单位: Arizona State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1531991&HistoricalAwards=false
• 关键词: MRI; Acquisition; Cryo; EM; Southwest

An award has been made to Arizona State University to fund an electron microscope for use in the biological sciences by many faculty and their students in the southwestern region of the United States. The instrument will be housed in an existing regional electron microscope facility and supported by existing technical staff. The classroom and remote lecture courses and practical instruction currently offered in biological electron microscopy at ASU will be extended to include the more advanced and higher resolution cryo-electron microscopy techniques of which this machine is capable, while the internationally recognized ASU hands-on Winter School in high-resolution electron microscopy, offered annually since 1984 and heavily oversubscribed, will be expanded to cover this field. The next generation of scientists and educators, including groups under-represented in STEM fields, will be actively recruited and enrolled and will benefit significantly from the new research projects and funding made possible by acquisition of this instrument. The new cryo EM facility will provide three-dimensional images with exquisite fidelity of the molecular machines and protein molecules responsible for life on earth. These images will provide structural knowledge that is fundamental to attainment of the new understanding needed to improve the development of new drugs, new organic photovoltaics for solar energy, new sensor molecules, and better understand how proteins function (in viruses, cells, and tissues). This profound expansion of penetrating vision will give new eyes to scientists attempting to understand the origin and fundamental mechanisms present in many diseases (including afflictions such as Alzheimer's disease) and will lead to a parallel understanding of the function of living tissues, for example, revealing deeper understanding of how the signaling and protein molecules in human muscles work. Further expanding this impact, cryo EM will enable research at the intersection of state of the art science and environmentally sustainable practices through contributions to research that monitors the safety of nanomaterials deposited in the environment.The research undertaken using this new cryo EM facility will mainly be based on "single-particle cryo-electron microscopy", a method which allows three-dimensional images of the molecules of life to be recorded at such high magnification that the individual atoms in the molecules can be seen (in favorable cases). This enables proteins and other nanoscale biological structures molecules to be imaged without having to be first crystallized (as in conventional crystallography). When possible, leaping beyond this tedious trial-and-error process, which sometimes takes many years, or in some cases may never be possible, is a true game-changer in structural biology. By studying the way atoms are arranged in molecules, scientists can improve the effectiveness of drugs, reduce side effects, and also understand how the molecular machines on which life is based operate. In addition, new methods for imaging molecules will be developed including methods based on electron-beam scattering from protein nanocrystals, the development of new phase-plates for electron beams, and the use of new scanning probe microscopy modes to obtain three-dimensional images of entire cells, normally considered too large to be imaged in the electron microscope.

亚利桑那州立大学获得了一项奖励，以资助美国西南部地区的许多教师和学生在生物科学中使用电子显微镜。该仪器将安置在现有的区域电子显微镜设施中，并由现有的技术人员提供支持。目前在ASU提供的生物电子显微镜的课堂和远程讲座课程和实践教学将扩展到包括更先进和更高分辨率的冷冻电子显微镜技术，而国际公认的ASU动手冬季学校自1984年以来每年提供高分辨率电子显微镜，并严重超额认购，将扩大到涵盖这一领域。 下一代科学家和教育工作者，包括在STEM领域代表性不足的群体，将被积极招募和注册，并将从新的研究项目和获得该工具所提供的资金中受益匪浅。新的低温EM设备将提供负责地球生命的分子机器和蛋白质分子的精确逼真的三维图像。这些图像将提供结构知识，这是实现新的理解所需的基础，以改善新药物的开发，新的太阳能有机光致发光材料，新的传感器分子，并更好地了解蛋白质的功能（在病毒，细胞和组织中）。这种深入的视野扩展将为科学家提供新的视角，试图了解许多疾病（包括阿尔茨海默病等疾病）的起源和基本机制，并将导致对活组织功能的平行理解，例如，揭示对人类肌肉中信号和蛋白质分子如何工作的更深入理解。进一步扩大这一影响，cryo EM将通过对监测沉积在环境中的纳米材料的安全性的研究做出贡献，实现最先进的科学和环境可持续实践的交叉研究。使用这种新的cryo EM设施进行的研究将主要基于“单粒子冷冻电子显微镜”，一种能在高放大率下记录生命分子的三维图像的方法，这种放大率能使分子中的单个原子被看到（在有利的情况下）。这使得蛋白质和其他纳米级生物结构分子能够成像，而不必首先结晶（如传统的晶体学）。在可能的情况下，跳出这个繁琐的试错过程，这有时需要许多年，在某些情况下可能永远不可能，是结构生物学中真正的游戏规则改变者。通过研究原子在分子中的排列方式，科学家可以提高药物的有效性，减少副作用，并了解生命所依赖的分子机器如何运作。此外，还将开发新的分子成像方法，包括基于蛋白质纳米晶体电子束散射的方法，开发新的电子束相位板，以及使用新的扫描探针显微镜模式来获得整个细胞的三维图像，通常认为这些细胞太大而无法在电子显微镜中成像。