Richard Henderson was in a seminar when he got the call. It was from his friend and colleague Gunnar von Heijne, head of the Center for Biomembrane Research, Stockholm University, and director of the Cryo-EM Swedish National Facility. Von Heijne wasn’t calling to chat or get expert scientific input though—he represented the Nobel Committee for Chemistry.

“Gunnar only said ‘hold on one moment,'” Henderson says. “He put me through to a conference room, so I was on one end and the entire Nobel committee was on the other.'”

The committee gave him the news: Henderson, a structural biologist at the Medical Research Council Laboratory of Molecular Biology (MRC LMB), Cambridge, United Kingdom, would share the 2017 Chemistry Nobel Prize with Jacques Dubochet and Joachim Frank. The trio were honored for cryoelectron microscopy (cryoEM), which generates high-resolution views of structures such as proteins, viruses, and ribosomes.

Physics + biology expertise

Born in Scotland, Henderson arrived at MRC LMB as a graduate student in 1966. Except for postdoctoral work in the 1970s, he has remained there, including serving as director from 1996 to 2006. He originally studied physics, moving to molecular biology early in his career. That dual training served his research well, since his work requires a deep understanding of the physics of imaging and the biology of cells.

Henderson’s contribution to cryoEM began with his work with Nigel Unwin. In 1975, they published a landmark study on the structure of the seven-transmembrane protein bacteriorhodopsin. Their breakthrough was using electron microscopy instead of x-ray crystallography to model the protein. In 1990, Henderson published a higher resolution bacteriorhodopsin structure using methods developed by his research group. Since then, he has worked to advance electron microscopy for structural biology, including serving on task forces for best practices, data management, and archiving.

If you heard a lot about cryoEM even before the Nobel news, it’s because of recent advances in the field. Earlier, electrons were detected indirectly by film or modified cameras.

“The big impact four or five years ago,” Henderson says, “was new direct electron detectors that made images much clearer and less noisy. They increased resolution by a factor of two.”

Additional improvements in image processing brought cryoEM resolution to the single-digit angstrom range. CryoEM is also now more user friendly. Compared to 10 years ago, Henderson says, instruments are “more automated, more stable, and easier to use.” 

CryoEM for drug discovery

CryoEM has applied as well as basic science uses, Henderson says, for example in drug discovery and development. “Quite a few facilities around the world are using cryoEM,” he says, “to find where drugs bind and to develop better medicines.”

Henderson is on the board of Heptares Therapeutics and was a cofounder in 2007. The company now has 150 employees and was bought by the pharmaceutical company Sosei. Heptares focuses on G protein-coupled receptors, which are seven transmembrane-domain proteins with the same general structure as bacteriorhopsin. The receptors are attractive targets for structure-based drug design because they implicated in diseases from cancer to Alzheimer.

The MRC LMB encourages translational science, Henderson says, based in part on great success with humanized monoclonal antibodies, which are used therapeutically for cancers, Ebola, and other diseases.

We’ve had more than 30 years of strong tech transfer.

“Alongside research and advancing knowledge, part of our remit is to identify applications from ideas that emerge from our research, and patent or license them or start companies,” he says. “We’ve had more than 30 years of strong tech transfer.”

Having colleagues who knew the pros and cons of patenting, licensing, and creating a company was invaluable for the Heptares founders. Just when they needed them, Henderson says, “The MRC had a number of people with prior experience who gave us good advice.”

Democratizing cryoEM

With the Nobel award, Henderson has a more visible public platform. He’s using it to promote what he calls “a bit of a crusade” that he and others have been on to “democratize cryoEM.” Demand is already high at cryoEM facilities, and will probably increase as the Nobel Prize brings attention to the method. However, a top-of-the-line microscope can cost EUR 5 million. Henderson and colleagues are working to make the method more widely accessible.

“We’ve been trying to persuade the three main companies that sell high-end ‘scopes to sell lower-cost instruments,” he says. “They all say they’re interested, although they’re not so keen when we say we need one that costs 10 times less.”

A backup plan is to upgrade the thousands of existing older cryoEM instruments with newer detectors and electron sources. They won’t be as automated as newer models, but will help Henderson’s democratization project towards its goal: giving scientists at smaller universities and research groups access to cryoEM. Henderson says another model is public-private cryoEM facilities. For example, in his city of Cambridge, a group of pharmaceutical companies installed a shared cryoEM instrument at a university and allow academic researchers to use it on weekends.

As access to cryoEM grows, it will continue to integrate into the selection of methods available to structural biologists.

We’re in a golden era for structural biology.

Henderson doesn’t subdivide his area by technologies, but says, “In our field, we’ll use any method to find a structure and we have a lot of tools: NMR spectroscopy, x-ray crystallography—and cryoEM.”

In fact, Henderson says, for proteins that will form sufficiently large crystals, high-throughput robotics make it possible to get hundreds of x-ray crystallography structures a day, compared to about one per day for cryoEM. With an array of methods to choose from, you can get the structure of just about anything, he says: “We’re in a golden era for structural biology.”