Genomic Science Program
U.S. Department of Energy | Office of Science | Biological and Environmental Research Program

2023 Abstracts

Laboratory for BioMolecular Structure: A DOE-Funded National Cryo-EM Center

Authors:

Liguo Wang* ([email protected]), Guobin Hu, Jake Kaminsky, Qun Liu, and Sean McSweeney

Institutions:

Brookhaven National Laboratory

URLs:

Goals

The Laboratory for BioMolecular Structure (LBMS) at Brookhaven National Laboratory (BNL) provides peer-reviewed research access, support, and training for the use of cryo-electron microscopy (cryo-EM). Cryo-EM has been widely employed to determine biomolecular structures and the establishment of LBMS makes it possible for the research community to advance the foundational knowledge of the biological complexity of plant and microbial metabolism and their interfaces. A key goal for LBMS is to attract DOE-BER sponsored researchers to take advantage of LBMS’ cryo-EM and help them in all phases including project initiation, sample preparation, data collection, processing, and interpretation. Three tiers of trainings are offered to teach new users so that they can conduct independent research later and to ensure experienced users get the very best data possible at LBMS. The LBMS also establishes a culture of innovation to extend the state-of-the-art through exploring new methods of sample preparation, data collection and analysis, and automation leading to an improvement in throughput and accuracy of the structures determined.

Abstract

To advance understanding of biological processes and complexity, cryo-electron microscopy (Cryo-EM) has become a preferred method for studying structures of biological macromolecules and high-order machinery. However, for many institutions and research groups, acquiring and operating a state-of-the-art cryo-EM facility remain cost prohibitive. With the joint support from the New York State and the Department of Energy (DOE), the Laboratory for BioMolecular Structure (LBMS) at Brookhaven National Laboratory, a national cryo-EM center, provides cutting-edge instruments and operations for imaging biological structures and processes. LBMS provides merit-based, no-cost access to non-proprietary users as well as cost-recovery access to proprietary users.

The mission of LBMS is to accelerate fundamental understanding about the building blocks and their functions in all living organisms. LBMS strives to foster expeditious developments in biotechnology and medicine to meet the Nation’s urgent needs in biofuels and healthcare. LBMS fulfills its mission by offering training and access to highly advanced cryo-EM capabilities to the broad research community. In 2022, LBMS supported 92 users to collect 809,032 images, and 71 structures were been determined. Ten papers were accepted/published and fourteen manuscripts are under review. LBMS also offers trainings to current and potential users. In addition to in-person trainings for sample preparation and screening, and remote training for data collection on the high-resolution EM, the team hosted the second annual cryo-EM course that was attended by ~400 attendees from 24 countries. For current and potential LBMS users, the team organized four quarterly cryo-EM workshops that focused on practical aspects of cryo-EM techniques and involved intensive interactions among instructors and attendees. The average rating of the workshops is 4.5/5.0 and 100% of the attendees will recommend the workshops to others.

To support users to perform their best achievable research, LBMS explores and optimizes emerging methods of instrumentation, sample preparation (negative staining, vitrification, cryo-focused ion beam milling), data collection (single particle analysis, cryo-electron tomography), data analysis, and automation. LBMS is a user-centric facility with excellence through user training, user support, instrument operation, and facility development.

Funding Information

Brookhaven National Laboratory is managed by Brookhaven Science Associates for the U.S. Department of Energy under contract no. DE-SC0012704. This program is supported by the U. S. Department of Energy, Office of Science, through the Genomic Science Program, Office of Biological and Environmental Research, under FWP KP1607011.