Biophysics Collaborative Access Team

Biophysics Collaborative Access Team

Research Emphasis

The Biophysics Collaborative Access Team (BioCAT) has constructed and now operates facilities at Argonne National Laboratory=s Advanced Photon Source as a national research resource for the study of the structure of partially ordered biological molecules, complexes of biomolecules, and cellular structures under conditions similar to those present in living cells and tissues. The goal of research at BioCAT is to determine the detailed structure and mechanism of action of biological systems at the molecular level. The techniques used are X-ray fiber diffraction, X-ray solution scattering, and X-ray microemission and microabsorption spectroscopy, with an emphasis on time-resolved studies and development of novel techniques.

Current Research

X-ray diffraction of biological fibers for study of regulatory mechanisms in various types of muscle, including cardiac muscle, structure of collagenous tissues; viruses; amyloids; and membrane/protein systems. Solution scattering of proteins and nucleic acids; ligand-protein interactions; structure of complexes; time-resolved protein folding. Microemission spectroscopy of cells and tissues to provide elemental maps and spectroscopic information that can be related to neurodegenerative diseases, cancer, or developmental processes. Instrumentation development. Novel detector designs. Improved data acquisition, data evaluation, and robust data analysis methods.

Resource Capabilities

Small and wide angle X-ray fiber diffraction, Small and wide angle X-ray solution scattering of proteins and nucleic acids. Emission and absorption hard X-ray spectroscopic mapping (resolution: <5 micron) of cells and tissues.

Instruments

Advanced Photon Source undulator A beamline, fixed exit height, cryogenically cooled silicon monochromators, energy range of 3.5B15 KeV Si(111), and 8B35 KeV Si(400) using the first harmonic, up to 70 KeV with the second harmonic of Si(400); one-meter-long harmonic rejection/vertical focusing mirror, crystal horizontal sagittal focusing. Rapid crystal change with dual monochromators. Rapid energy scanning capability. Measured flux at 7 KeV is ~2 times 10¹³ photons/sec into a focal spot that is vertically adjustable between <40 microns to ~1 mm vertical and horizontally adjustable from <180 microns to ~4 mm with full beam flux. Independent horizontal and vertical focus. Smaller beams (micron scale) are available at reduced flux. Small-angle X-ray scattering (SAXS) camera. Ionization chambers, silicon drift detectors, large acceptance multilayer and Laue analyzer/detector for fluorescence X-ray absorption fine structure and microprobe, high-sensitivity/spatial resolution charge-coupled device detectors for SAXS and fiber diffraction.

Software

Workstations with data analysis software for microemission spectroscopy and SAXS and fiber diffraction.

Available Resources

Well-equipped biological sample preparation and characterization laboratory adjacent to beamline; electronics laboratory.

Training Opportunities and Workshops

Periodic training workshops and hands-on "Small Angle X-ray Scattering workshops.

Publications

1. Caliskan, G., Hyeon, C., Perez-Salas, U., Briber, R. M., Woodson, S. A., and Thirumalai, D., Persistence length changes dramatically as RNA folds. Physical Review Letters 95:268303–1–268303–4, 2005.

2. Dickinson, M., Farman, G., Frye, M., Bekyarova, D., Gore, D., Maughan, D., and Irving, T., Molecular dynamics of cyclically contracting insect flight muscle in vivo. Nature 433:330–333, 2005.

3. Fischetti, R. F., Rodi, D. J., Gore, D. B., and Makowski, L., Wide-angle X-ray solution scattering as a probe of ligand-induced conformational changes in proteins. Chemistry and Biology 11:1431-1443, 2004.

4. Jacob, J., Krantz, B., Dothager, R. S., Thiyagarajan, P., and Sosnick, T. R., Early collapse is not an obligate step in protein folding. Journal of Molecular Biology 338:369-382, 2004.