Duke University and UNC-Chapel Hill didn’t add to their roster of Nobel Prize laureates in chemistry on Wednesday, but they’re working hard to make sure their professors have direct access to the technology this year’s trio of winners helped develop.
In concert with the Research Triangle Park-based National Institutes of Environmental Health Sciences, the universities are making seven- and eight-figure investments to buy, install and operate “cryo-electron microscopy” equipment that can reveal the structure of organic molecules down to the atomic level.
“We’re going from nothing to three instruments,” said Leslie Parise, chairwoman of the UNC-CH medical school’s Department of Biochemistry and Biophysics and one of the prime movers behind her institution’s end of the project.
The NIEHS already has one of the microscopes up and running, while Duke has taken delivery on another that remains in its crate pending completion of the lab it’ll occupy. UNC-CH has a third “that’s on order,” Parise said.
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Eventually, the institutions will operate the instruments as a consortium, putting requests for analytical runs through a scientific board with representatives from each that among other things will make sure the samples researchers are sending in for study are good enough to work with.
Duke’s microscope has the highest resolution of the three and will ultimately become the preferred tool for projects that need its capabilities. The UNC-CH and NIEHS machines have or will have somewhat lower resolution, making them what Parise termed “very good screening instruments” that can handle “most of the samples coming” their way.
The collaboration’s come together over the past couple of years, with momentum developing at both institutions after refinements of sensor technology in 2013 yielded a big increasing in resolving power.
But “like everything else, it’s taking longer than we wanted or initially thought,” said Robert Lefkowitz, a Duke biochemist who shared the 2012 Nobel in chemistry for his work on protein receptors.
He, Parise and Duke School of Medicine biochemistry chairman Richard Brennan all were eager to talk about the project Wednesday after the administrators of the Nobels announced in the morning that they’ve awarded this year’s chemistry prize to British scientist Richard Henderson, German-born professor Joachim Frank and Swiss biophysicist Jacques Dubochet.
Each made critical contributions to the development of “cyro EM” technology, with Henderson being the first to use it to produce atomic-resolution images, Frank developing the computational techniques that go into assembling the images and Dubochet figuring out the best way to deep-freeze samples so they’re suitable for analysis.
Their work so stands out that the Nobel was “not really” a surprise, Lefkowitz said, adding that one of his graduate students, Anthony Nguyen, had asked him point-blank on Monday whether he thought Henderson, Frank and Dubochet would get the 2017 prize.
“I said, ‘You know, given the events of the last year, I’m coming around,’” Lefkowitz said, recalling Nguyen’s query.
Given the advances in sensor technology, those events include the fact that universities and research institutes around the world are now scrambling to get their hands on one of the microscopes. There still aren’t many of them around, and until now Triangle researchers have had to collaborate with colleagues elsewhere in the U.S. and the world if they wanted to use cryo EM in their work.
The technology is potentially an enormous help to everything from basic science to drug development work because it allows researchers to see not just the structure of a molecule, but the way other substances bind themselves to it, Lefkowitz and Brennan said.
But in terms of university politics, it has a big drawback. “It’s expensive, it truly is,” Brennan said.
Lefkowitz said the all-in cost of establishing a cryo EM facility is “north of $10 million,” plus hundreds of thousands of dollars a year in additional operating costs.
At Duke, getting involved took support from Chancellor for Health Affairs Eugene Washington and then-dean of medicine Nancy Andrews, Lefkowitz and Brennan said.
Down the road at UNC-CH, Parise and other supporters of the project assembled about $6 million, mostly from the departments and schools on campus that have a stake in biochemical research. The N.C. General Assembly kicked in $525,000 as part of the state’s fiscal 2017-18 budget.
The NIEHS lined up a former National Institutes of Health cryo EM expert, Mario Borgnia, to head the consortium and get its own machine up and running.
Duke is also planning to add faculty linked to the project, specifically someone capable of pushing the bounds of imaging technique, Brennan said, adding that the university wants to develop in-house expertise and has “probably about 10 faculty members who can move into cryo EM very quickly.”
The project is significant enough at Duke that Andrews made a point of highlighting it in her final state-of-the-medical-school speech to faculty in March. She termed it both “outrageously expensive” and “critically important” for the university.
Brennan likewise said Duke’s leaders are fully on board. “My view – and I think Duke has this view – is it’s expensive, but it’s not a cost,” he said. “It’s an investment.”
Lefkowitz, who helped lobby campus leaders for the project, said the push for it “was a bottom-up thing” that originated with the faculty. He added that in a career at Duke that began in 1973, he has noted that the university has been “slow, over and over again, to adopt cutting-edge technologies.”
“And that’s hurt,” he said. “Even with cryo EM, we’ve sort of been late to the party. We certainly have not been in the first wave.”
But Parise said the latest developments in sensor resolution are what tipped the scales at her institution.
“I’ve been chair of the Department of Biochemistry and Biophysics for going on 11 years,” she said. “When I first walked into the department, I had people telling me about cryo EM, and I have white papers [on it] going back that far. But about four years ago, there was a real improvement in the technology ... and it became integral to planning. The excitement reached a level where the time was right, and the investment was made.”