Introduction. Many of the advances in structural molecular biology and related biosciences are the result of the rapidly occurring developments at synchrotrons. These include X-ray crystallography for protein structure determination, X-ray spectroscopy for examination of metalloprotein structure, and synchrotron footprinting technologies for examining macromolecular structure and dynamics. The Case School of Medicine of Case Western Reserve University recently established the Case Center for Proteomics and Mass Spectrometry, for expanding the state-of-the art in proteomics research. This center provides administrative oversight for the Case Center for Synchrotron Biosciences (CSB) which is funded by the National Institute of Biomedical Imaging and Bioengineering (NIBIB) as a Biotechnology Research Resource to serve an international community of biomedical scientists. The CSB is catalyzing further development and application of synchrotron radiation tools through a number of multidisciplinary collaborations and partnerships among an international community of scientists. The research facility located at the National Synchrotron Light Source (NSLS) at the Brookhaven National Laboratory (BNL) in New York. The NSLS, as a Department of Energy funded facility, has as a mission to provide academic institutions access to synchrotron light through various collaboration and consortium arrangements.
What is a Synchrotron?
Synchrotrons are accelerator facilities that provide extremely high flux and high brightness electromagnetic radiation at energies ranging from the infrared, through the ultraviolet, to the X-ray regions for investigating the structure of matter. The storage ring at the NSLS is designed to maintain "bunches" of electrons in a circular orbit, the energies of 2.8 GeV on the X-ray ring and 750 million electron volts on the Vacuum Ultraviolet-Infrared ring. These electron bunches are maintained in the circular orbit by a series of bending magnets that are equally spaced around the 170 meter circumference of the ring. As the electrons traverse the magnetic fields, they are accelerated or "bent" to maintain the orbit, and in the process photon energy is given off over a wide frequency range. Thus, at each of the 40 bending magnets found around the ring (and at selected straight sections), beam ports are placed (up to three can co-exist side by side for each magnet) to allow the radiation to pass safely in a confined vacuum space to an experimental chamber. The photon energy spectrum given off depends on the characteristics of the bending magnet, and most beamlines on the X-ray ring provide X-ray radiation in the energy range from 4,000 to 20,000 electron volts (0.8-3Å wavelength). For biologists, this radiation provides opportunities to conduct experiments in X-ray Imaging, Crystallography and diffraction, small angle scattering, X-ray Spectroscopy, and X-ray Footprinting. The Vacuum Ultraviolet-Infrared ring is similar in overall design, but is smaller (51 meters circumference), operating at lower energies, and provides ultraviolet and infrared light.
The Synchrotron Biosciences Projects at CSB. The use of synchrotron technologies for research in the biomedical sciences at the NSLS has undergone rapid growth. The research activities at CSB are mainly dedicated to the fields of microscopy, spectroscopy, hydroxyl radical footprinting and crystallography. The microscopy is used to image cells and tissues by utilizing an IR spectroscopy source; X-ray Absorption Spectroscopy yields the information about chemistry of biomolecules, mainly, the chemistry of metalloproteins and their active sites. Crystallography is used to determine the three dimensional structures of macromolecules and nucleic acids at atomic resolution by structural genomics and structural biology investigators; hydroxyl radical footprinting coupled with mass spectrometry (for proteins) or gel analysis (for nucleic acids) is used to study the dynamics of large macromolecular complexes, protein-protein interactions and protein-nucleic-acid interactions.
Goals. A decade ago, the technologies and facilities suitable to study one protein at a time and one gene at a time were the state-of-the art. Now, novel high-throughput technologies have changed the situation where multiple genes and proteins can be studied simultaneously. CSB has been instrumental in the development and implementation of a number of novel technologies for high- throughput and quality research in the field of Structural & Molecular Biology. The goal of the CSB is to enhance the research efforts of in-house faculty and provide unique and powerful research tools to assist investigators across the US and around the world in pursuing their current grant programs as well as assisting them in the pursuit of new awards. Furthermore, the novel structural proteomics technologies developed at the CSB will be dedicated to core, collaborative and service projects for international community of biomedical scientists.
