BER Structural Biology and Imaging Resources
Synchrotron, Neutron, and Cryo-EM
U.S. Department of Energy | Office of Science | Office of Biological and Environmental Research

Advanced Light Source

DOE scientific user facility sponsored by the Office of Basic Energy Sciences

Lawrence Berkeley National Laboratory

The Advanced Light Source (ALS) is a specialized particle accelerator that generates bright beams of x-ray light for scientific research. Electron bunches travel at nearly the speed of light in a circular path, emitting ultraviolet and x-ray light in the process. The light is directed through about 40 beamlines to numerous experimental endstations, where scientists from around the world (“users”) can conduct research in a wide variety of fields, including materials science, biology, chemistry, physics, and the environmental sciences. Operation of the ALS is funded by the U.S. Department of Energy, Office of Basic Energy Sciences. It cost $99.5 million to build.

The wavelengths of the synchrotron light span the electromagnetic spectrum from infrared to x-rays and have just the right size and energy range for examining the atomic and electronic structure of matter. These two kinds of structure determine nearly all the commonly observed properties of matter, such as strength, chemical reactivity, thermal and electrical conductivity, and magnetism. The ability to probe these structures allows us to design materials with particular properties and understand biological processes inscrutable to visible light.​

Structurally Integrated Biology for the Life Sciences (SIBYLS)

The SIBYLS beamline is a dual end station synchrotron beamline combining macromolecular crystallography (MC) with small-angle X-ray scattering (SAXS). MC produces high-resolution structural information from biological molecules, and the high-throughput SAXS pipeline enables the same biological systems to be imaged in aqueous solution, closer to their natural state. Combining SAXS results with atomic-resolution structures provides detailed characterizations of mass, radius, conformation, assembly, and shape changes associated with protein folding and functions. SAXS also can resolve ambiguities of crystallography by showing the most likely possible structures.

Berkeley Synchrotron Infrared Structural Biology (BSISB) Program

BSISB provides facilities and training supports for characterizing cellular chemistry and function by synchrotron radiation–based Fourier transform infrared (SR-FTIR or sFTIR) spectromicroscopy, time-resolved sFTIR spectromicroscopy, synchrotron Infrared Nano-Spectroscopy (SINS), and 3D synchrotron FTIR micro-tomography (sFTIR µTomography). Other complementary microscopy and spectroscopic imaging methods include fluorescence microscopy, Raman microscopy, and simultaneous optical hyperspectral sample imaging. Aqueous environments hinder sFTIR’s sensitivity to bacterial activity, but BSISB’s integrated in-situ microfluidic systems circumvent the water-absorption barrier while allowing cells to maintain their functions. These systems have enabled real-time chemical imaging of bacterial activities in biofilms and facilitated comprehensive understanding of structural and functional dynamics in a wide range of microbial systems. BSISB continues to build new chemical imaging capabilities, advance user-specific microfluidic systems and automation, and develop new software and machine learning for accelerating data analysis.

National Center for X-Ray Tomography (NCXT)

NCXT is leading the development of soft X-ray tomography (SXT) as a technique for imaging fully hydrated biological specimens at high, three-dimensional (3D) spatial resolution. SXT has several distinct advantages over light- and electron-based microscopies and, as a result, can contribute unique insights on cell structure and behavior. Soft X-rays penetrate biological materials much more deeply than electrons, allowing cells up to 15 µm thick to be imaged intact. SXT image contrast is generated by differential X-ray absorption by biomolecules, meaning that cells advantageously do not require exposure to staining or other potentially damaging procedures prior to being imaged. Consequently, SXT produces high-resolution specimen views that are in a close-to-native state.

SXT’s utility has been increased dramatically by the concomitant development of high-aperture cryogenic fluorescence tomography (CFT). Cryo-preserved cells, or populations of cells, can now be imaged serially by two disparate tomographic methods. The combination of CFT and SXT allows labeled molecules to be positioned accurately and viewed directly in the context of a high-resolution, quantitative 3D tomographic cell reconstruction.

  • Location: Advanced Light Source, Lawrence Berkeley National Laboratory, Berkeley, CA
  • Website: NCXT
  • Points of contact: Carolyn Larabell (
  • Access procedure: Through the ALS User Office, but please call or email the points of contact if you have any questions or want to discuss the feasibility of your experiments.
  • Overview brochure
  • Feature stories on NCXT website: NCXT Highlights

Macromolecular Crystallography (Co-located facility at the ALS)

The Advanced Light Source is home to several macromolecular crystallography (MC) beamlines. This technique can be used to visualize molecules at atomic resolution, enabling protein engineering, the design of therapeutics, and the fundamental understanding of enzyme mechanisms and protein function. The Berkeley Center for Structural Biology operates 5 MC beamlines (5.0.1, 5.0.2, 5.0.3, 8.2.1 and 8.2.2) for industrial and academic users. The Molecular Biology Consortium operates beamline 4.2.2 for academic users. The University of California operates beamline 8.3.1 for its researchers. The beamlines provide robotic systems for crystal handling and remote access for data collection.