RII Track-4:NSF: Enhancing Structural Science in the Rocky Mountain Northwest Through Microcrystal Electron Diffraction (MicroED)

揭示分子的原子组成及其随后的三维结构，是许多研究项目的关键所在。绘制分子原子结构的方法多种多样，但最近的进展激发了创新技术，使更复杂的结构研究成为可能。该奖学金将使培训快速发展的冷冻电子显微镜（CryoEM）方法称为微晶体电子衍射（MicroED）。MicroED利用与x射线晶体学相同的衍射现象来绘制分子图。然而，MicroED使用电子，允许在x射线衍射所需尺寸的十亿分之一的晶体上收集数据。使用这种消失的小晶体有助于解决小分子和大分子x射线晶体学的共同障碍-获得大尺寸的单晶材料。这一特点将激发MicroED方法的进一步改进，该技术最终将成为结构解析研究的常用选择。培训将通过教育材料的管理得到加强，这将使未来几代结构科学家受益，并促进这一新兴技术的价值。本提案的主要目标是让PI获得领导和进行MicroED实验以阐明分子结构的能力。通过远程学习和合作访问国家低温系统访问和培训中心（NCCAT）， PI和两名学员将获得从基础理论方面到数据展示的MicroED分析整个过程的全面指导。该项目将以研究为导向，重点研究卤素键低聚物和对胆碱酯酶8A （RIC-8A）蛋白抑制剂的抗性。小分子和大分子研究反映了MicroED研究的多样性，并将确保不同范围的研究人员可以利用PI的新MicroED技能集。研究结果和教育材料将通过外联、出版物和讲习班传播，向各种专门知识的听众介绍这项技术。PI最终将提供MicroED服务，在未来几年加强蒙大拿大学和周围EPSCoR机构结构科学家的研究工作。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Revealing the atomic makeup of molecules, and their subsequent 3-dimensional structure, is at the crux many research programs. Methods for mapping the atomic structure of molecules are diverse, yet recent advancements have inspired innovative techniques making more complex structural studies possible. This fellowship will enable training in a rapidly developing cryo-electron microscopy (CryoEM) method called microcrystal electron diffraction (MicroED). MicroED maps molecules using the same diffraction phenomena as X-ray crystallography. However, MicroED employs electrons which permits data collection on crystals about a billionth of the size needed for X-ray diffraction. Using such vanishingly small crystals helps address a common obstacle of small molecule and macromolecular X-ray crystallography—achieving sizable single crystalline materials. This feature will motivate further refinement of MicroED methods, and the technique will ultimately become a common option for structure elucidation studies. The training will be reinforced by the curation of education materials that will benefit future generations of structural scientists and promote the value of this emerging technique. The primary objective of this proposal is for the PI to acquire the ability to lead and conduct MicroED experiments to elucidate molecular structures. Through remote learning and collaborative visits to the National Center for CryoEM Access and Training (NCCAT), the PI and two trainees will obtain comprehensive instruction on the entire process of MicroED analysis from fundamental theoretical aspects through to data presentation. The project will be research driven, focusing on both halogen bonding oligomers and the resistance to inhibitors of Cholinesterase 8A (RIC-8A) protein. The small molecule and macromolecular studies reflect the diversity of MicroED studies and will ensure that a diverse range of researchers may take advantage of the PI’s new MicroED skillset. The results and educational materials will be disseminated though outreach, publications, and workshops, exposing the technique to audiences of varied expertise. The PI will ultimately provide MicroED services, enhancing the research efforts of structural scientists at the University of Montana and surrounding EPSCoR institutions for years to come.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.