Dr. Jessica Bruhn

Principal Scientist
NanoImaging Services

Jessica Bruhn, PhD
Scientific Group Leader, MicroED
NanoImaging Services

My formal training is in X-ray crystallography (Scripps Research Institute) and single-particle CryoEM (Salk Institute) applied to the structural and functional analysis of proteins and macromolecular complexes. I joined NanoImaging Services (NIS), a leading provider of CryoEM and TEM services, in 2019 where, amongst other projects, I have been spearheading our microcrystal electron diffraction (MicroED) development efforts. MicroED is a novel structure determination method capable of determining structures from crystals orders of magnitude smaller than those required for single-crystal X-ray diffraction (~0.2-2μm). This method is especially attractive for those working in the pharmaceutical small molecule space as crystallization screening and optimization can be completely eliminated in many cases when MicroED is employed. This greatly reduces the time and material required for structure determination, as well as expands the types of compounds/polymorphs that can be structurally characterized by crystallography.

Over the past two years we have developed a reliable pipeline for MicroED structure determination including sample preparation, data collection and data processing (DOI: 10.3389/fmolb.2021.648603). A particular focus of mine has been on automating and streamlining as many of these steps as possible, including adapting Leginon to collect high quality MicroED data and automating several of the data processing steps. In January 2020, NIS officially launched MicroED structure determination services for small molecules of interest to the pharmaceutical industry and we have now collected data from over 70 small molecule samples. In 2021 we were awarded an SBIR grant from the NIH/NIGMS to further our MicroED development efforts and address some of the challenges that remain to be solved including absolute configuration determination, expanding our workflow to handle crystals that are only stable in the crystallization solution, improving data quality and applying better methods for phasing. I really look forward to seeing how this novel method improves over time and how it is applied to accelerate/improve pharmaceutical development.