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

RII Track-4：NSF：通过微晶电子衍射 (MicroED) 增强落基山脉西北部的结构科学

• 批准号: 2132227
• 负责人: Daniel Decato
• 金额: $ 15.48万
• 依托单位: University of Montana
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2132227&HistoricalAwards=false
• 关键词: RII; Track; NSF; Enhancing; Structural

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.

揭示分子的原子组成及其随后的三维结构是许多研究计划的关键。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。该奖学金将使培训在一个快速发展的低温电子显微镜（CryoEM）方法称为微晶电子衍射（MicroED）。MicroED使用与X射线晶体学相同的衍射现象来绘制分子。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。使用这种微小的晶体有助于解决小分子和大分子X射线晶体学的一个共同障碍，即获得相当大的单晶材料。这一特点将促使MicroED方法的进一步完善，该技术最终将成为结构解析研究的常见选择。培训将通过教育材料的管理得到加强，这些材料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。该提案的主要目标是PI获得领导和进行MicroED实验以阐明分子结构的能力。通过远程学习和对国家冷冻EM访问和培训中心（NCCAT）的合作访问，PI和两名学员将获得从基本理论到数据呈现的MicroED分析整个过程的全面指导。该项目将以研究为导向，重点关注卤素键合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，并将确保各种研究人员可以利用PI的新MicroED技能。将通过外联活动、出版物和讲习班传播成果和教育材料，向具有不同专门知识的受众介绍这一技术。PI最终将提供MicroED服务，在未来几年内加强蒙大拿大学和周围EPSCoR机构的结构科学家的研究工作。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估来支持。