Drs. Alberto Bartesaghi and Mario Borgnia Have Major Breakthrough in Cryo-Electron Tomography

Drs. Alberto Bartesaghi and Mario Borgnia Have Major Breakthrough in Cryo-Electron Tomography

Their collaboration lasted roughly a year and a half, meeting weekly to perfect what would be a breakthrough in cryo-electron tomography (ET). Dr. Alberto Bartesaghi, Associate Professor in Biochemistry and Computer Science at Duke University and Dr. Mario Borgnia, Director of the Cryo-EM Core at the NIEHS were on a mission to render a hi-resolution, 3D image of the tiniest of proteins. Current microscopic techniques weren’t practical—data collection was too slow and when sped up, produced poor resolution. 

The principle by which cryo-ET visualizes proteins inside cells is similar to a CT Scan. But alike in their outcome, they are opposite in how they get there. With a CT Scan, the detector moves, taking images from multiple views. In cryo-ET, the detector remains fixed, and the plate where the sample sits rotates. Jonathan Bouvette, a postdoc in the Borgnia Lab, wrote the computer code that tells the microscope to take multiple images at different degrees of plate tilt, and Hsuan-Fu Liu, a PhD student in the Bartesaghi Lab, developed the computational algorithms to obtain the high-resolution structures. 

There are three reasons their discovery, published this month in Nature Communications, is exciting for future research and the cryo-ET community—they scanned the smallest sample ever, in the shortest time ever, at the highest quality ever. Since the majority of biomedically relevant targets are small proteins, solving their structure within the native cell environment is critically important to future drug design. And speeding up data collection by reducing the number of days it takes to render a 3D image from ten to one not only saves time and resources but makes structural studies of drug targets under natural conditions possible.