$4.6 million from NIH puts CWRU Synchrotron lab on track to become No. 1 in world

Case Center for Synchrotron Biosciences assembles cutting-edge new beamlines at Brookhaven National Laboratory in Upton, N.Y.

Case Western Reserve University’s synchrotron facility at Brookhaven National Laboratory is on its way to becoming the No. 1 beamline facility for biology in the world by early 2016, thanks to a jumpstart grant of $4.6 million from the National Institute of Biomedical Imaging and Bioengineering (NIBIB), a component of the National Institutes of Health (NIH). For two decades, the Case Center for Synchrotron Biosciences has developed and operated beamlines for an international community of users. These advanced instruments deliver ultra powerful x-rays that allow scientists to visualize in action the nano-scale structures of the body’s molecules and proteins. Armed with these meticulous images, scientists attempt to pinpoint disease-causing vulnerabilities in the body’s molecules and proteins and target those weaknesses for therapeutic intervention. To prepare for the upgrade, the four existing beamlines of the center, located at the National Synchrotron Light Source (NSLS) at Brookhaven laboratories in Upton, N.Y., went offline Sept. 30 while construction continued on the new synchrotron light source (The NSLS-II), right next door. During the last two years, $50 million from NIH, the National Science Foundation and the U.S. Department of Energy have been invested at Brookhaven to fund the construction of four new state-of-the-art beamlines at NSLS-II for the biological science user community. The recent award of $4.6 million from NIBIB to Case Western Reserve University will support the commissioning and operation of the beamlines allowing the re-start of user operations for both CWRU scientists and investigators from across the world.

“When NSLS-II opens, the lab’s beamlines will have the brightest, most intense x-ray beams—100 times brighter than beamlines anywhere in the world,” said Mark Chance, director of the Center for Proteomics and Bioinformatics at the  School of Medicine. “With this technology, NSLS-II will collect data 100 times faster than any other synchrotron facility in the world.” NIBIB also welcomes the research capabilities of the new beamlines at NSLS-II. “We look forward to this new light source coming online and giving clarity to the molecular machines that are the inner working components of cells,” said Christina Liu, program director of Molecular Imaging at NIBIB. The National Science Foundation (NSF) has entered the act as well. In 2012, the NSF awarded the Case Center for Synchrotron Biosciences a $4 million grant toward building a particularly specialized beamline dedicated to footprinting. With footprinting, the beamline provides highly detailed visualization of the structure and dynamics of biological macromolecules. Macromolecules are the “machines” of the cell, and footprinting at a synchrotron beamline enables scientists to identify key moving parts of the machine at the level of single nucleotides or amino acids that make up this molecular entity. Scientists can then view how molecular structures interact and move within a solution (liquid) state, often within living cells. “These new beamlines will provide the tip of the spear, as I call it—the really razor-sharp, cutting-edge stuff,” Chance said. “Now we will be able to view intact whole complexes of proteins at one time. In the past, we could usually pull out one protein at a time and solve its structure, but then it was unclear how these proteins assembled and interacted together.” Until NSLS-II becomes operational in early 2016, no beamlines will be available at Brookhaven. However, beginning this fall, the Case Center has partnered with beamline facilities on the West Coast to serve the interim needs of scientists who had relied on the Case Western Reserve facility. These efforts will keep together the strong scientific communities that have evolved throughout the years to use these facilities productively. For the past 20 years, the Case Center for Synchrotron Biosciences has served hundreds of institutions and accommodated the beamline research needs of more than 400 scientists. Since 2003, these scientists from around the world have published more than 1,100 papers using the Case Western Reserve-based facilities. “Nearly 20 percent of the users of our beamline services over the years have been Case Western Reserve research investigators from Cleveland, including dozens of principal investigators,” Chance said. The Case Center for Synchrotron Biosciences has even offered a mail-in program where scientists shipped their protein crystal or protein solution samples to the NSLS lab for beamline analysis. The service saved investigators travel time and enabled beamline facilities to run at optimum capacity. The mail-in service also provided smaller labs access to beamline technology that might not have been available otherwise. “This outreach and dissemination of our beamline technology helps grow the field,” Chance noted. Synchrotron services are in wide demand throughout the world as beamlines become standard tools for scientists to investigate the structure and function of all kinds of matter. Australia, Taiwan, Canada and Singapore all have synchrotron beamlines, and China is in the process of building several more. Forty percent of synchrotron users worldwide come from the biology field. Materials science studies of surfaces and polymers and studies of chemical catalysis represent another 40 percent of beamline demand, while physics research comprises the remaining 20 percent. A scientific niche that particularly relies on synchrotron technology is structural biology with its vast work in crystallography. With crystallography, scientists take a newly discovered protein and arrange its atoms or molecules into a visible crystal. The crystal is then exposed to the intense x-rays of the beamline, and the ways in which the crystal bends the x-rays are analyzed to understand the intimate details of the protein’s structure. “Through the newer, cutting-edge beamlines, it will be possible to obtain a good signal from lousy crystals,” Chance said. “Crystals that were once impossible to obtain a structure from previously will become merely difficult.” Examining the intricacies of crystal structures is particularly important for membrane proteins on the surface of cells that transmit critically important signals for body function and represent the most important drug targets to investigate for new medicines. “The biggest impact of improving crystallography is deciphering these incredibly difficult membrane proteins and the complicated assemblies of multiple proteins that govern how a cell functions,” Chance said. “By discovering the key ‘moving parts’ in these crystal structures of one or more proteins, we could develop targeted therapies to counter the disease-causing frailties in these structures.”