Cryo-EM Explained: Visualizing Life’s Machinery

Joseph Kim (left) and Elizabeth Wright (right) sit at computers to monitor data collection at a Krios microscope. Glass windows showcase the microscope room in the background.

The world of the super-small — of proteins, ribosomes, bacteria, viruses, and other biomolecules — is perpetually abuzz inside of us and around us. To understand how this world works, we need to see it up close and in motion. For ever-closer access to life’s machinery, scientists are increasingly drawing on a powerful structural biology technique called cryogenic electron microscopy, or cryo-EM.

Cryo-EM helps us visualize the molecular world, such as the machinery fueling the synthesis of telomeres in humans. Here, accessory protein called CST binds a DNA template and positions the central cog in the DNA replication machine for RNA synthesis. Image: Ci Ji Lim

The University of Wisconsin–Madison is at the forefront of cryo-EM research. The university is home to two cryo-EM research centers that support investigators from around the United States: the Cryo-EM Research Center (CEMRC), which opened in 2021, and the Midwest Center for Cryo-Electron Tomography (MCCET), which opened in 2022. The centers are directed by biochemistry professor Elizabeth Wright.

The data yielded through cryo-EM imaging is critical to advancements in drug discovery and vaccine development, energy research, and more. Yet, exactly how cryo-EM data results in high resolution images of life’s molecular makeup is complex.

A new explainer by science communicators at the Morgridge Institute for Research and the Department of Biochemistry decodes the nuanced world of cryo-EM technology, methods and research. Learn more here.