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The Frederick National Laboratory will host a new training program in Frederick, Maryland, September 12-16 for cancer researchers who want to build expertise in cryo-electron microscopy (cryo-EM). 

Cryo-EM is a microscopy technique where samples are flash-frozen and bombarded with electrons to generate images. The resulting high-resolution images are helping cancer researchers solve the structures of proteins and other biological macromolecules. The in-person training is designed to broaden the use of cryo-EM and help address the shortage of qualified personnel to conduct the studies. 

“The power of cryo-EM lies is in its ability to study biological macromolecules in near physiological conditions as they interact with one another, act on substrates and make reaction products or bind small molecules,” said Jana Ognjenović, Ph.D., team lead of the Advanced Cryo-EM Technology Group. “The method allows researchers to probe the dynamics accompanying a biological process and to computationally sort out multiple coexisting conformational states.” 

Ognjenović's group supports the National Cancer Institute’s National Cryo-EM Facility at the Frederick National Laboratory by focusing on projects with the potential to make cryo-EM a more widely accessible technique. 

“This unsurpassed wealth of information, often drawn from a single sample, will be pivotal for understanding cancer development and progression, improving current therapies and developing novel approaches to treating this disease,” she said.  

Filling a gap

Historically, the expense of the microscopy instruments was the major barrier preventing greater adoption of this powerful technique. To address this need, the National Cancer Institute established the National Cryo-EM Facility at the Frederick National Laboratory in 2017, providing no-cost imaging to cancer researchers who lack access to these multi-million-dollar microscopes at their own institutions. To date, the facility has completed more than 700 imaging sessions from over 50 institutions. 

“The advent of the resolution revolution in cryo-EM is still only about 10 years old and as a result, there has been a flood of interest in investigators wanting to add cryo-EM to their experimental toolbox, but a lack of qualified experts to undertake these experiments,” said Thomas Edwards, Ph.D., senior microscopist at the National Cryo-EM Facility. “We hope that additional training workshops such as this one will help close that gap in expertise.”  

This training program represents a critical next step in establishing standard practices and making cryo-EM accessible to the research community. 

“For many research areas, state-of-the-art resources are a critical element to obtaining high-quality data,” Ognjenović said. “In the case of cryo-EM, you have the additional factor that the equipment is incredibly sensitive and complex, and it is a challenge to find scientists who have the necessary expertise to operate the microscope optimally. Even the surrounding room environment can influence the microscope and therefore the outcome of the experiment. Further, decisions about data collection settings and specimen selection often require judgment calls that can have a profound effect on the data quality.” 

Intensive training

The new training program offers five days of immersive and hands-on training at the Frederick National Laboratorys Advanced Technology Research Facility. It will cover grid preparation, screening, data collection, image processing, model building, and validation.  

Trainees will have the opportunity to learn from experts working in the field—Frederick National Laboratory scientists and invited speakers. There is no registration fee, but the application process is competitive. Applicants should have access to cryo-EM equipment through their institution.  

The first cohort will consist of 12 trainees. Applications will open March 15. 

“Structural biology is in the midst of a resolution revolution, led by incredible advances in cryo-EM technology,” said Leonard Freedman, Ph.D., Frederick National Laboratory’s chief science officer. “The challenge is to help the extramural community keep up with such technology, and as a national lab, we view training in cryo-EM as a critical component to our mission and that challenge.”