A New Era for Structural Biology at Northwestern
University acquires next-generation cryo‑electron microscope, accelerating breakthroughs in biology and medicine
Northwestern University is greatly expanding its capabilities in structural biology and biomedical discovery with the acquisition of a state-of-the-art Krios cryo-electron microscope, which is now being prepared for use.
Funded by a $15 million gift from the Sherman Fairchild Foundation, the instrument provides a new window into the building blocks of life. It also marks a major milestone in advancing one of Northwestern’s top research priorities: strengthening the biosciences through increased collaboration between the Evanston and Chicago campuses and fostering transformative interdisciplinary work.
Expected to be available to University researchers in April, the Krios joins Northwestern’s powerful ecosystem of instrumentation spanning multiple core facilities—including existing cryo‑EM platforms such as a Glacios microscope in FACET in Chicago and a Glacios microscope in the Structural Biology Facility, where the Krios will be housed, and advanced imaging tools primarily for materials research within NUANCE—further strengthening the University’s integrated capabilities.
A Revolution in Visualizing the Molecular Machinery of Life
Cryo–electron microscopy, or cryo-EM, has revolutionized how scientists visualize the tiny molecules that make life work. Using this technique, researchers can determine detailed 3D structures of proteins, DNA, RNA, and large molecular machines that play essential roles in health and disease. (Pictured above: Cryo–electron microscopy reveals the atomic details of apoferritin, a hollow, spherically shaped protein complex that stores iron.)
At its core, cryo-EM works by flash-freezing biological molecules in a thin layer of ice. This rapid freezing preserves the molecules in a state that closely approximates their natural structure, without the need for chemical fixes or crystallization. The frozen samples are then placed inside a powerful electron microscope. A beam of electrons interacts with the sample, generating thousands to millions of 2D images of individual molecules, each captured from a slightly different angle.
Advanced computer algorithms analyze and combine these many images to reconstruct a highly detailed 3D model, much like assembling a 3D object from countless snapshots. Because the molecules are frozen so quickly, scientists can visualize them in near-native conformations, with minimal distortion from preparation.
For decades, X-ray crystallography was the dominant method for determining molecular structures, but it requires molecules to form well-ordered crystals, a slow and often challenging process. Cryo-EM bypasses the need for crystallization, complementing techniques like crystallography and enabling the study of many molecules that are difficult or impossible to crystallize.
Major technological breakthroughs in the early 2010s—including more stable microscopes, ultra-sensitive electron detectors, and powerful image-processing software—sparked what scientists call the “resolution revolution.” Cryo-EM images improved from low-resolution outlines to near-atomic detail. These advances were recognized with the 2017 Nobel Prize in Chemistry and now drive progress across biology and medicine. Cryo-EM plays a key role in drug development and has been critical for rapid public-health responses—most notably enabling scientists to determine the structure of the SARS-CoV-2 spike protein during the COVID-19 pandemic.
A Transformative New Capability for Northwestern Researchers
Northwestern currently uses mid-range Glacios microscopes for screening samples and preliminary work. However, the absence of a high-end Krios has limited the pace and scope of cryoEM-enabled projects across at least eight departments at Northwestern. The arrival of the Krios completely changes that landscape. The Krios will operate alongside the Glacios, which remain essential for sample screening, grid optimization, and researcher training.
“Adding a Krios unlocks experiments our scientists simply cannot do today,” said Alfonso Mondragón, Ethel & John Lindgren Professor of Molecular Biosciences and director of the Structural Biology Facility, a shared resource of the Lurie Comprehensive Cancer Center and the location of the new instrument. “It positions Northwestern to pursue discoveries at the frontiers of molecular science and to support researchers working on some of the most challenging biological problems.”
Mondragón’s own research focuses on molecular “tools” such as topoisomerases—enzymes that untangle DNA and help maintain healthy cellular function, and non-coding RNA molecules. His work illuminates fundamental mechanisms of life and supports the development of new therapeutic strategies.
Expanding Impact Across Campuses and Disciplines
Northwestern scientists already harness cryoEM to generate high-impact insights. For example, Molecular Biosciences faculty members Juan Du and Wei Lü use the technique to visualize mechanisms of sensory perception, including taste and temperature. The work has implications for the treatment of pain and metabolic diseases. Other scientists across the Weinberg College of Arts and Sciences and the Feinberg School of Medicine, including the groups of Heather Pinkett, Paul DeCaen, Murali Prakriya, and Smriti Sangwan, apply cryoEM to elucidate protein mechanisms, identify targets for therapeutics and antimicrobial drugs, and investigate ion channels and receptors implicated in human disorders and immune function.
“The Krios also dramatically enhances the training opportunities for our students and postdoctoral researchers,” said Weinberg Family Distinguished Professor of Life Sciences and Chair of Molecular Biosciences Amy Rosenzweig, who uses cryoEM to study methane-consuming enzymes that can be used for biomanufacturing.
“CryoEM has transformed how scientists study protein structure and function, which has also enabled structure-guided drug discovery. The new Krios microscope will propel Northwestern research in exciting new directions that can lead to therapeutic breakthroughs for cancer, brain disease, and other conditions with unmet medical need,” said Alfred L. George, Jr., M.D., A.N. Richards Professor and Chair of Pharmacology in the Feinberg School of Medicine.
A Strategic Investment in Talent and Discovery
The Krios will strengthen Northwestern’s leadership in advancing human health by enabling scientists to visualize biology with unprecedented clarity. Because leading peer institutions now operate multiple Krios microscopes, this investment is also crucial for competitiveness. As part of Northwestern’s shared facilities network, which includes SBF, FACET, NUANCE, and specialized imaging platforms across both campuses, the Krios adds new capabilities while ensuring researchers have the right instrument for every stage of a project.
“This acquisition is a scientific and strategic investment,” said Provost Kathleen Hagerty. “The Krios will help us attract top talent, boost cross-campus collaboration, and accelerate discoveries that benefit society.”
The gift from the Sherman Fairchild Foundation marks a transformative investment in Northwestern’s scientific enterprise. “This extraordinary gift will have a generational impact on science at Northwestern,” said Vice President for Research Eric Perreault. “With the Krios, our researchers will be able to see and understand biology in entirely new ways, expanding what is possible and accelerating discoveries that will shape the future of medicine.”
—Matt Golosinski