COVID-19 News

BNL's cryo-electron microscopes debut early for COVID-19 research

On July 29, the Department of Energy’s (DOE) Brookhaven National Laboratory opened a new cryo-electron microscopy center, the Laboratory for BioMolecular Structure (LBMS), with an initial focus on COVID-19-related research.

This state-of-the-art research center for life sciences imaging offers researchers access to advanced cryo-electron microscopes (cryo-EM)—funded by New York State—for studying complex proteins, as well as the architecture of cells and tissues. Researchers working on COVID-19-related studies can request free access to the instruments using a simple proposal process. LBMS operations are funded by the DOE's Biological and Environmental Research program.

Many modern developments in biology, medicine, and biotechnology have been made possible through the understanding of how biological structures such as proteins, tissues, and cells interact with each other. But to truly reveal their function as well as the role they play in diseases and medical conditions, scientists need to visualize these structures at the atomic level. Cryo-EM offers scientists a way to image biological structures with high resolution to accelerate advances in research fields including drug discovery, biofuels development, and medical treatments.

The project team rose to the COVID-19 challenge by accelerating the original construction schedule, enabling the facility to open access for COVID-19-related research two months ahead of schedule. LBMS currently has two cryo-electron microscopes—funded by $15 million from NY State’s Empire State Development—and the facility has space for additional microscopes to enhance its capabilities in the future. In recognition of NY State’s partnership on the project and to bring the spirit of New York to the center, each laboratory room is associated with a different iconic New York State landmark.

Researchers from the lab’s Biology Department will be the first to use the new facility. This group has been studying recombinant proteins from the novel coronavirus for several months.

“Partnering with LBMS allows us to access a suite of cutting-edge tools and expertise to define structures of proteins. In the future, we will use these microscopes to study not only COVID-19-related samples but also other protein complexes, integrating these studies with our biochemical genetic experiments performed in Biology Department labs,” said Biology Department Chair John Shanklin. “This will allow us to contribute to the DOE mission by defining mechanisms underlying processes related to the production of biofuels and bioproducts.”

Biology Department researchers will work closely with Liguo Wang, Scientific Operations Director of the LBMS, to study the parts of the virus using the new cryo-EMs.

“Based on recent studies, we know that the coronavirus consists of four major structural proteins: the spike (S) protein, nucleocapsid (N) protein, membrane (M) protein, and the envelope (E) protein,” Wang said. "In collaboration with Brookhaven’s Biology Department, we will study how the E and M proteins form the viral particle and investigate the structure of the N protein. Our results will help to understand how the virus works and, therefore, how we can fight it.”

In addition to working with his colleagues at Brookhaven Lab, Wang will also set up and run experiments for researchers from other institutions across the country and around the world.

“We are accepting research proposals related to COVID-19 from both academia and industry,” he said. “Even though visiting researchers cannot come on site at this time, we can still accept their frozen samples and investigate them. Once a proposal receives time on our instruments and the samples have arrived, our staff will load them into the microscope and align it. Then, the researchers can either collect data remotely, or we can collect the data for them. Once collected, we can transfer the data to the researchers’ home institution or process it in collaboration with the researchers using the LBMS’s computing resources.”

At the beginning of July, the new microscope produced its first image of a test sample, showing its high-resolution capabilities. In a cryo-EM, samples are maintained at a temperature of -274°F so the electron microscope can “photograph” individual molecules embedded in ice. Based on these images, scientists can create 3D models of the biological samples they are investigating.

Scientists using the LBMS’s capabilities will also benefit from the center’s close proximity to Brookhaven’s National Synchrotron Light Source II (NSLS-II), a DOE Office of Science User Facility and one of the most advanced synchrotron light sources in the world. NSLS-II enables scientists from academia and industry to tackle the most important challenges in quantum materials, energy storage and conversion, condensed matter and materials physics, chemistry, life sciences, and more by offering extremely bright light, ranging from infrared light to x-rays. The vibrant structural biology and bio-imaging community at NSLS-II offers many complementary techniques for studying a wide variety of biological samples.

“The strong partnership between NSLS-II and LBMS will offer researchers access to expert staff at both facilities as well as to a versatile set of complementary techniques,” said NSLS-II Director John Hill. “While x-ray crystallography can reveal very high-resolution images of small components, cryo-EM can reveal the structure of large protein complexes and organelles. When combined, the techniques yield a comprehensive understanding of the underlying biology. Looking to the future, 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.”

Beyond the combined capabilities and expertise that both NSLS-II and LBMS offer, researchers will have access to a variety of training opportunities provided by LBMS’ expert staff. Once LBMS is open to general users, access to the facility’s tools will be granted through a peer-reviewed proposal process based on scientific merit.

“By allowing science-driven use of our instruments, we will meet the urgent need to advance the molecular understanding of biological processes, enabling deeper insight for bio-engineering the properties of plants and microbes or for understanding disease,” said Sean McSweeney, Science Director of LBMS. “We expect to have the first call for general experiments in August.”

McSweeney said the facility has a bright future ahead.

“When completed, LBMS will play a key role in our vision for bioscience research and development. This center will provide under-one-roof access to techniques that will cover biological research from the molecular to the cellular level, providing state-of-the-art instruments for cryo-electron microscopy and cryo-tomography," he said. "Our impact is further strengthened by the proximity and collaboration with NSLS-II. In the future, I expect us to be recognized as a center of excellence for biological imaging as a result of our technical innovation and scientific impact.”

Read more: https://www.bnl.gov/newsroom/news.php?a=117344