The field of cryogenic electron microscopy (cryo-EM) exploded in popularity during the “resolution revolution” in the 2010s, leading to the 2017 Nobel Prize in Chemistry awarded to Jacques Dubochet, Joachim Frank and Richard Henderson “for developing cryo-electron microscopy for the high-resolution structure determination of biomolecules in solution.” Cryo-EM techniques such as single particle analysis (SPA) now allow structure determination of biomolecules at resolutions previously only reached by X-ray crystallography. Cryo-EM offers many new possibilities as it does not require protein crystallization and allows structural determination of large protein complexes imaged in frozen solution or even in the cellular environment.
However, there are still challenges in using cryo-EM; e.g., the screening process to differentiate promising samples from poor ones requires efficiency because microscopy time is becoming increasingly scarce with the continuous influx of new users. Structural studies of protein complexes that orchestrate dynamic cellular processes are often limited due to their inherent flexibility and dynamic nature and thus require high-throughput data collection strategies followed by extensive 2D classification schemes. Structure-based drug design using cryo-EM requires high-resolution/high-throughput imaging pipelines to produce density maps that can unambiguously identify a drug-binding pose. And proteins that are too small require methods that improve contrast for particle picking. Consequently, cryo-EM tools and workflows that allow efficient screening, processing and data collection are becoming increasingly vital, especially in attempts to solve important yet challenging structures.
To address the challenges presented in the expanding cryo-EM field, JEOL introduced the CRYO ARM 200 and 300 in 2017. These were the first 200kV and 300kV dedicated cryo-transmission electron microscopes by JEOL.
Emmanuel Smith, Senior Application Specialist for Cryo-EM, JEOL USA
I am a cryo-EM Applications Specialist for JEOL USA, providing user support for the JEOL CRYO ARM microscopes in North America. My background is in Structural Biology. I obtained my PhD in X-ray crystallography and structure-based drug design at the lab of Yu Chen at the University of South Florida. I did my postdoc research in cryo-EM at the lab of Daniela Rhodes at the Nanyang Technological University where I worked on telomere-binding protein complexes. I later worked as staff at two cryo-EM facilities before returning back to research at the lab of Tina Izard at the Scripps Research Institute Florida campus to study F-actin protein complexes using the first JEOL CRYO ARM 300 in the US. I have extensive experience in all aspects of the SPA workflow from sample preparation to data collection and analysis.
