Cryo-EM Facility under Construction At Brookhaven National Laboratory

Brookhaven National Laboratory has broken ground on its Laboratory of BioMolecular Structure (LBMS), a state-of-the-art research center for life science imaging. At the heart of the center will be two new cryo-electron microscopes (cryo-EM) designed to study biomaterials.

“Cryo-electron microscopy is a rapidly advancing imaging technique that is posting impressive results on a weekly basis,” says LBMS Director Sean McSweeney. “The mission of LBMS is to advance the scientific understanding of key biological processes and fundamental molecular structures.”

Modern developments in biology, medicine and biotechnology have been made possible by research tools that visualize biological structures at the atomic level. Such advancements, according to the Brookhaven team, are crucial for understanding the functions and roles that each one plays in disease, knowledge that often leads to discovery of new treatment drugs.

One technique that can produce such structures with atomic resolution is X-ray diffraction, though it requires that molecules first be crystallized. The process is often time-consuming and sometimes impossible, so many important families of biological molecules remain poorly understood, according to Brookhaven.

Cryo-electron microscopy solves such challenges because the technique works on individual molecules and therefore does not require crystallization.

Samples are maintained at -274°F using liquid nitrogen in cryo-EM, and then individual molecules are photographed by an electron microscope. This capability has enabled scientists to study many new molecules for the first time with atomic resolution.

The cryo-EMs at LBMS, for example, will allow scientists to resolve complex molecular structures with unprecedented detail. Access to such tools will be granted through peer review proposals and extended to successful applicants without charge.

Scientists at LBMS will also benefit from the center’s close proximity to the National Synchrotron Light Source II, which creates some of the brightest X-rays in the world. Researchers can also use the ultrabright for complementary studies—such as protein crystallography—to yield more comprehensive sample views.

“The combination of the advanced research tools at NSLS-II and LBMS will offer researchers a versatile set of complementary techniques to study biological systems,” says NSLS-II Director John Hill. “While crystallography can reveal very high-resolution images of small components, cryo-EM can reveal the structure of large protein complexes but at lower resolution.”

According to Hill, when combined, the techniques yield a comprehensive understanding of the underlying biology. “Looking to the future,” Hill says, “we expect to combine other X-ray techniques with the cryo-EM data to provide unprecedented information on the structure and dynamics of the engines of life.”

At the start of operations, LBMS staff will provide researchers with a wide range of training opportunities, including day-to-day coaching as well as assistance with sample preparation, data collection and data processing. Further training and advanced workshops with leading experts will be offered to users to enable autonomous access to the cryo-EMs.

LBMS is expected to reach full functionality in 2020, while training opportunities will begin in 2019. Brookhaven expects the center’s wide variety of resources to attract scientists from around the world, providing a significant boost to New York, a state that contributed $15 million for the facility’s cryo-EM. ■