A type of electron microscopy long considered inferior has made major advancements, allowing biologists to see the detailed workings of the building blocks of life. Key science funders are backing what some are calling a revolution in imaging technology.
For decades, cryo-electron microscopy, or cryo-EM, was a real underdog when it came to the ways biologists could examine tiny subjects like cells, viruses, and proteins. It was snarkily labeled “blob-ology” because of the blurry images it produced. But proponents stuck with it, and in the last 10, even five years, hardware and software advancements have totally flipped the script.
Cryo-EM is having a moment in the spotlight, offering new insights into how crucial biological structures function and potential applications related to viruses, bacterial infection, Alzheimer’s, and diabetes. It’s still early in the game, but the journal Nature called it the “research method of the year” in 2015, and structural biologists are saying it’s kicked off a new era in the field.
Private philanthropy is playing a role in cryo-EM’s rise, with major science funders funding new facilities and backing researchers at the forefront of the technique. Howard Hughes Medical Institute, in particular, has been in on the action, including a recent $4 million grant.
To get a quick sense of what the fuss is all about, for decades, a method called X-ray crystallography dominated as the preferred method to gain clear images of some of the basic components of life. By crystalizing molecules and firing X-rays at them, biologists could gain a better picture of their structures and how they function. Research using the technique yielded Nobel Prizes, with cryo-EM taking a backseat as the domain of relatively small groups of researchers.
But those teams were dogged, and made huge refinements in the technology, which involves trapping molecules in a thin layer of ice and shooting electrons at them to capture images (this is a pretty good little primer). In 2008, one team invented a sensor system that snaps images at 400 frames per second, records terabytes of data, and relies on complex software to stitch it all together into a 3D composite image. As a result, a whole new set of important and elusive biomolecules can be examined down to their near-atomic structure.
As a result, Nature reported that in 2015, cryo-EM was used to map more than 100 molecules, and research teams are eager to get beam time at facilities. Imaging equipment is an expensive investment, after all, and top facilities are often long distances away.
Of course, the National Science Foundation is funding new facilities, including a $3.2 million grant to Arizona State University and $2.7 million to Cornell in 2016 alone. But some of the country’s biggest private science funders are also involved.
In one recent example, HHMI is providing a big chunk of funding for a new, state-of-the-art facility that will open at UMass Medical School (UMMS) in Worcester, Mass. The lab features two cryo-EM systems, funded with $4 million from HHMI and $5 million from a quasi-public state investment agency.
It’s a unique arrangement that partners up UMMS and Harvard Medical School, but also other schools like Boston University, and private entities like Novartis and Pfizer. The center is meant to serve the greater region’s universities and biotech firms alike.
HHMI, a world leader in biomedical funding, actually has multiple connections to the research method. The funder takes the unique approach of putting researchers directly on its payroll while they work at their universities, and also building its own research facilities. Both have come into play with cryo-EM.
So some of the leaders in supercharging the technology, including Yifan Cheng and David Agard, who worked to advance the camera systems at UC San Francisco, are both HHMI investigators. Eva Nogales of Berkeley is another HHMI investigator working at the forefront of the cryo-EM work. And HHMI investigators Melissa Moore, Craig C. Mello, and Phillip Zamore of UMass were instrumental in bringing the new facility to the school.
HHMI also opened its own research facility in 2006, Janelia Research Campus located in Virginia, and one of its priorities is developing new imaging technology. The campus has two cryo-electron microscopes, and is looking to expand the related services it can offer, according to its website.
But HHMI isn’t the only science funder supporting this type of work. Another of the largest research funders in the country, the Simons Foundation, is funding a project similar to the facility in Massachusetts, but for New York. In 2014, Simons committed $15 million to the New York Structural Biology Center to upgrade its cryo-EM facility. NYSBC is a consortium of nine research institutions founded in 2002 to create a cooperative imaging center.
Also located in New York, Rockefeller University was able to purchase new cryo-EM tools for the study of structural biology thanks to a grant from the EGL Charitable Foundation, a philanthropy connected to a university trustee.
Microscopy facilities, like massive telescopes, are ripe for science philanthropy. Especially early on, they require fairly large capital investments, but can unlock a whole set of future advancements from a variety of players. It just doesn’t always make sense for each institution that wants to pursue emerging techniques to buy all the gear. I like to use the analogy of the new iPhone dropping when you’re not eligible for an upgrade yet. A funder can spot you the $700, or, as the case may be, $4 million.
There’s also the fact that many teams can take advantage of this equipment. A funder can make a one-shot philanthropic investment that can make a region into a hub for research and industry.
HHMI’s Janelia campus is a unique example of a funder building its own lab, but these broad partnerships like the Massachusetts project are wrangling many interested parties and funding sources that will collectively lay the groundwork for years of future groundbreaking research in basic science and diseases.