Although the invention of the microscope already rapidly changed how scientists view the world, an enhancement algorithm developed by a multi-institutional team could further revolutionize the scientific world by allowing clearer 3D molecular maps to be observed by microscopes.
Developed by a team of researchers from institutions such as the New Mexico Consortium and Lawrence Berkeley National Laboratory, this computer algorithm sharpens molecular maps generated from cryo-electron microscopy, or cryo-EM. A microscopy technique that uses a beam of electrons to examine biomolecular structures, cryo-EM is quickly becoming the dominant technique used to determine 3D structures of macromolecules, according to the study published by the research team.
“With any experimental method, there’s typically noise. There are errors in your measurements that lead to getting an image that is not perfect,” said Paul Adams, co-author and director of the Molecular Biophysics and Integrated Bioimaging division at Berkeley Lab. “This algorithm is designed to try to remove some of those errors and try to get a clearer image.”
The algorithm’s modification procedure combines existing information of what molecules should look like with experimental data to produce sharper molecular maps, according to Adams.
Although this idea is not new, originating from other fields including crystallography and astronomy, Adams said the team of researchers was the first to provide evidence that the method works for cryo-EM.
“The big thing here was to apply it to electron microscopy because it hadn’t been done before,” Adams said. “People didn’t actually know whether it could be done; a lot of people thought it couldn’t be done.”
One of the main challenges of the research, according to Adams, was modifying the technique as it was used in crystallography to the field of microscopy.
Although the end results of crystallography and microscopy experiments are similar, the details of the noise are different. A lot of work went into understanding the difference in the two procedures and adapting the technique for cryo-EM use, Adams said.
“It’s only really in the last five years that that technique has really taken off as a way to look at biological molecules,” Adams said. “It’s going to be a very important technique in the future.”
The team hopes that this cryo-EM technique will help scientists interpret microscopy data and obtain clearer molecular maps for future biological understanding and discovery, Adams said.
Adams added that electron microscopy techniques will have important implications for human health — for example, they are currently being used to study COVID-19.
“These are very important things that actually affect people’s lives, ultimately,” Adams said. “We hope in some small way, by getting people better pictures of what they’re trying to understand, that they’ll be able to do a better job.”