Visualizing Biological Systems at the Molecular and Cellular Level at the Laboratory for BioMolecular Structure
Authors:
Liguo Wang* ([email protected], PI), Guobin Hu, Jake Kaminsky, Qun Liu, Sean McSweeney
Institutions:
Brookhaven National Laboratory
Abstract
Cryo-electron microscopy (cryo-EM) is a powerful imaging technique used to visualize biological specimens; it has experienced exponential growth in the past decade, marking a ‘resolution revolution’. Currently, there are more than 32,000 entries of EM maps and other results in the Electron Microscopy Data Bank. In addition to the atomic structures of biological macromolecules, cryo-EM has been employed to study protein-protein and protein-cell interactions and offers insights into cellular and tissue organizations at a resolution unsurpassed by other imaging techniques. This technique plays a pivotal role in advancing scientists’ insight into biological processes at the molecular and cellular level.
With the establishment of the Laboratory for BioMolecular Structure (LBMS), Brookhaven National Laboratory provides peer-reviewed research access, support, and training for the use of cryo-EM. By allowing science-driven use of these instruments, LBMS meets the urgent need to advance the molecular understanding of biological processes, enabling deeper insight and opening the possibility to engineer biological functions in a predictable fashion. Last year, LBMS supported more than 100 sessions, and collected more than one million cryo-EM images, which resulted in 116 high-resolution (better than 4 angstroms) structures and 15 publications.
LBMS also offers three-tiered trainings to current and potential users: (1) annual four-day cryo-EM course to the public; (2) quarterly cryo-EM workshops for current and potential LBMS users; (3) on-demand five-day training for LBMS users, either in person on screening EMs or remote training on the high-end EM, as needed. The average rating of the workshops is 4.4 out of 5.0, with 91% of participants indicating they would recommend the workshop to others.
In recent years, cryo-electron tomography (cryo-ET) has garnered increasing attention due to its unique capability for direct visualization of interactions between complexes in their cellular environment. It offers unparalleled insights into molecular organization, cellular structure, and cell physiology, making it a powerful tool for probing intricate details at the nanoscale within a cellular context. To expand the cryo-ET capability at LBMS, the team will establish and operate a cryo-ET user program to support a broad range of projects funded by DOE. Three distinct routes will be offered based on the nature of the sample and the specific regions of interest. With the development of the cryo-ET program, researchers can study cells/ organelles and tissues. This bridges a critical imaging gap in the biomedical size spectrum, connecting studies of molecules at atomic resolution to cellular and tissue investigations.