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

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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.