We propose to develop a Biological Small-angle X-ray Scattering (BioSAXS) station for the Compact Light Source, a powerful new generation of X-ray sources, which will enable biologists and biochemists to pursue state-of-the-art research in macromolecular structure studies in their own laboratories. The frontier of structural biology is the determination of large macromolecular complexes-the machines that drive the workings of the cell. X-ray crystallography is the method of choice for revealing the structures of these complexes, and has had important successes. However, since many complexes have proven to be difficult or impossible to crystallize, alternative methods are required. Lower resolution methods like SAXS can provide overall shape information of the complex that can be used, together with known substructures, for modeling its architecture. The advent of synchrotron sources together with advanced computing has led to a renaissance for SAXS as a complementary technique to crystallography for understanding a variety of molecular complexes. By developing a BioSAXS beamline and endstation, the CLS will offer biologists a new tool to perform synchrotron-like quality SAXS in their own academic or research laboratories at resolutions currently unreachable using conventional source technology. The flux of this BioSAXS beamline will exceed presently available homelab SAXS beamlines by three orders of magnitude, providing results comparable to many productive SAXS beamlines at the synchrotrons. The BioSAXS beamline is expected to complement the existing crystallography endstation already developed for the CLS to provide a unique, combined product for leading-edge biophysical analysis.
Public Health Relevance Statement: Public Health Relevance: The proposed Biological Small-angle X-ray Scattering (BioSAXS) station for the Compact Light Source will provide a unique instrument for leading-edge biophysical analysis, allowing the structural study of proteins and other macromolecules which are hard to crystallize. This structural information is vital to understanding a molecule's biological function, and plays a critical role in understanding diseases or developing new drugs.
Project Terms: Architecture; base; beamline; Benchmarking; Biological; Biological Process; Cells; Collimator; Complement; Complex; Crystallography; Data; design; detector; Disease; Elements; Engineering; Environment; Equipment; experience; frontier; Future; Generations; Geometry; Goals; Grant; Image; instrument; Laboratories; Laboratory Research; Light; Macromolecular Complexes; macromolecule; Measurement; Mechanics; Methods; Modeling; Molecular; Molecular Structure; Motion; Noise; Optics; Output; Performance; Pharmaceutical Preparations; Phase; Play; protein structure; Proteins; prototype; public health relevance; Renaissance; Research; research study; Resolution; Roentgen Rays; Role; Sampling; Shapes; Signal Transduction; Small Business Innovation Research Grant; Solutions; Source; Specific qualifier value; Spottings; Staging; structural biology; Structure; success; Synchrotrons; System; Techniques; Technology; Testing; tool; Work; X-Ray Crystallography
