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BioCARS: A Synchrotron Structural Biology Resource

Keith Moffat, Ph.D.

Center Overview

BioCARS is a national user facility for synchrotron-based static and dynamic studies of biological macromolecules, located at the Advanced Photon Source, Argonne National Laboratory. The mission of BioCARS is to develop state-of-the art facilities and provide scientific and technical expertise and user support for studies of dynamic (and static) properties of macromolecules by X-ray scattering techniques such as crystallography, SAXS/WAXS and fiber diffraction. BioCARS operates two X-ray beamlines, embedded in a Biosafety Level 3 (BSL-3) facility. This BSL-3 synchrotron-based capability is unique in the US and permits safe studies of biohazardous materials, such as human pathogens.

Time-resolved x-ray crystallography is a unique tool that provides snapshots of molecules in action at atomic resolution. Given the dynamic nature of functioning molecules, such studies are extremely important in understanding how molecules perform their function. Time-resolved macromolecular crystallography has been the chief scientific mission at the BioCARS 14-ID beamline since the start of operation. BioCARS staff and users played a leading role in the development of the technique to its relatively mature status today.

In addition to advances in time-resolved crystallography, time-resolved solution scattering has been implemented at 14-ID. X-ray scattering snapshots over a broad range of q spanning 0.02-2.5 Α‾1 can be recorded, thereby providing simultaneous coverage of the small-angle X-ray scattering (SAXS) and wide-angle X-ray scattering (WAXS) regions. By providing insights into the global structural dynamics of macromolecules in their natural environment, time-resolved SAXS/WAXS studies complement and extend studies conducted by time-resolved X-ray crystallography. The technique is applicable to many biologically important systems in solution.

Impact on Human Health

The research conducted at BioCARS aims at solving transient and static, atomic-level macromolecular structures, many of which are of direct relevance to significant biomedical problems. Some structures are directly related to biohazards classified at the BSL-3 level; examples include human pathogenic viruses, such as West Nile virus, and prions. Others, such as anthrax-related toxins or enzymes, are key to the metabolism of pathogenic microorganisms. Such structures are of substantial public health interest.

In other studies, BioCARS users explore macromolecular dynamics and mechanism through static and time-resolved studies of fundamental processes such as catalysis, regulation and signal transduction. Understanding dynamics is essential to understanding function, but such studies also provide a novel view of mechanisms of action, and thus underlie the development of more effective therapeutic agents.