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High-resolution electron microscopy comes to Yale

October 11, 2017
High-resolution image of a Thermoplasma acidophilus 20S proteasome produced by Yale’s new Titan Krios. Image courtesy of Shenping Wu.

The arrival of the cryoelectron microscope heralds a new era in research and discovery.

The ability of Yale investigators to learn the characteristics of a biological specimen in brilliant detail has recently been greatly enhanced.

The Titan Krios cryoelectron microscope (cryo-EM) arrived on West Campus in January, was dedicated in June, and is now fully operational. As described by one structural biologist at the School of Medicine, its capabilities represent nothing less than a revolution, due to the ability it affords researchers to elucidate structures and biological processes that are the key to solving the most vexing diseases.

The Nobel Prize in Chemistry awarded this month to the three scientists most responsible for developing cryo-EM speaks volumes about the technology’s potential. In awarding the prize, the Royal Swedish Academy of Sciences stated that cryo-EM “has moved biochemistry into a new era.” It is my strong belief that some of the resulting innovations will originate here at Yale.

Cryo-EM is especially useful in obtaining atomic structures of membrane proteins, including the receptors and transporters that are the targets of many drugs. These have been particularly difficult to crystallize—a step that is required for X-ray crystallography—but cryo-EM methods do not require crystallization. The result has been an explosion in our ability to visualize structures in which an understanding of the details of drug binding will open the door to new therapeutic approaches. Cryo-EM is also well-suited for new studies involving gene regulation, RNA splicing, and protein folding.

The device Yale has purchased also brings cryoelectron tomography (cryo-ET)—an advance that builds upon cryo-EM—to our campus. Still in its relative infancy, this technique provides the ability to view specimens in three dimensions from multiple angles. Our scientists already are employing cryo-ET to investigate such varied areas as the complex interplay between the immune system and HIV, pathogens’ ability to travel through and harm the body, and potential strategies for thwarting bacterial infections that bypass increasingly unreliable antibiotics.

The presence of the Titan Krios additionally supports another of YSM’s top priorities—attracting the world’s most talented scientists to our ranks. We already have a number of outstanding investigators working in this area. With the addition of this extraordinary resource, our ability to recruit top faculty has received a substantial boost. We recently welcomed new faculty members with expertise in cryo-ET and cry-EM, as well as technical staff to support the use of this tool, which will benefit a broad range of studies.

It took vision and careful planning to bring this instrument to Yale—most notably by the late Carolyn W. Slayman, deputy dean for academic and scientific affairs, and by Steven Girvin, who until recently was the university’s deputy provost for science & technology. Their efforts were supported by many of our faculty who collaborated on this endeavor.

Yale has had a distinguished history in structural biology, based on decades of world leadership in X-ray crystallography. Although cryo-EM will not supplant X-ray work, the preparation of samples for cryo-EM and cryo-ET is often less painstaking, and, importantly, less specialized. When more of our brightest minds can take advantage of such an advanced piece of technology as the Titan Krios, our ability to conduct groundbreaking research is magnified exponentially. That is an exciting prospect both for discovery at Yale, and for patients afflicted by disease whose lives we are now better positioned to improve.