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Research expands crystallography abilities by Cindy Abole Public Relations Imagine the possibilities as MUSC researchers are capable of conducting real-time research using cutting edge technology from more than 750 miles away. It’s already happening with synchrotron technology and research involving a handful of X-ray crystallography experts and other structural biology researchers working at MUSC.      Biochemistry graduate student Neil Demarse and Dr. Alena Fedarovich, members of Dr. Chris Davies' lab, evaluate data.   Christopher Davies, Ph.D., associate professor, Department of Biochemistry and Molecular Biology and director of MUSC’s X-ray Crystallography Shared Resource, and his research team successfully demonstrated the use of a new network connection linking MUSC to the Advanced Photon Source, Argonne National Laboratory in Chicago on Nov. 21. This allowed MUSC researchers access to a synchrotron beamline to perform valuable crystallography experiments that may lead to new drug discoveries or cures for diseases.      X-ray crystallography is one of only two experimental techniques that can provide detailed pictures of biological molecules at atomic-level resolution. The other is nuclear magnetic resonance spectroscopy (NMR), which involves collecting diffraction patterns from crystals and using them to decipher three-dimensional structures.   The test, using remote access and newly developed robotics, was part of a program affiliated with a 25-member consortium of universities, private industry, the National Aeronautics and Space Administration, and the National Institutes of Health, known as South-East Regional Collaborative Access Team (SER-CAT). SER-CAT was established a decade ago by world-renowned X-ray crystallographer Bi-Cheng Wang, Ph.D., at the University of Georgia, to enhance X-ray crystallography research capabilities among affiliated crystallographers, structural biologists and researchers at institutions based in the Southeast.   Internationally, SER-CAT is recognized as one of the best beamlines available to scientists today. Other popular beamline facilities are located at Brookhaven National Laboratories (New York), Stanford University (California) and Louisiana State University.   The technology uses highly intense X-rays to determine 3-D structures of macromolecules, such as proteins, DNA, RNA, or protein-DNA/RNA complexes, by a method known as multiwavelength anomalous dispersion (MAD). Synchrotron radiation also reveals such structures at a greater level of detail than can be obtained on the “home-source” of X-rays.   Previously, the only way to access synchrotron beamlines was to travel to these facilities and perform such experiments in person. However, such trips were both time consuming and costly, thus allowing only a small number of investigators to be involved. Within the last three months, MUSC has demonstrated its new capability to acquire such data remotely across the network by accessing and controlling the crystal-handling robotics and beamline computers at the SER-CAT facility.  This provides a more timely analysis of crystals while opening the door to collaboration between any investigator at MUSC and cutting-edge experiments.   “Through this effort we can solve and understand protein structures and use these to address important biomedical problems,” said Davies. “Gaining remote access to the SER-CAT beamline is a significant development for our X-ray crystallography program at MUSC because it brings multimillion dollar technology directly to our doorstep at virtually zero cost.”   “Over time, this will enhance the spread of crystallography studies at MUSC since more users can participate in structural studies,” said Yusuf Hannun, M.D., Ralph F. Hirschman Professor and Chairman, Department of Biochemistry and Molecular Biology. “Structural studies constitute a major way of the future for biomedical research. Structural biology provides the ‘ultimate’ resolution for any basic research project, and it also is essential for drug development, understanding various pathobiologic problems. MUSC is fortunate to have Dr. Davies to lead this effort.”      To set up the remote-access system and prepare for the inaugural test, Davies and his team turned to Brian Muller and Mary Mauldin, Ed.D., Associate Professor and Director of Educational Technology, both of the MUSC Library’s Center for Academic Research Computing, plus support staff from the University of Georgia (UGA) and SER-CAT, to install, test and activate access control software on a local PC. Prior to the test, the team shipped cryofrozen crystals to SER-CAT for on-site staff to place in the storage Dewar of the crystal-handing robot at the beamline. Investigators at MUSC then instructed the robot to transfer a crystal from the Dewar to the X-ray beam and proceeded to collect diffraction data. These data were used to determine the structure of a bacterial enzyme bound with a candidate antimicrobial compound.      “An important step in the drug discovery pathway is to obtain a high-resolution image of the molecular target for that drug. We’re much more likely to get that quality of information using data collected from crystals at the synchrotron than in our labs,” Davies said.     In the future, such experiments will benefit from recent improvements in network connectivity. In 2006, the Argonne National Laboratory, SER-CAT, University of Georgia and the Southern Light Rail successfully demonstrated a new high-speed, direct point-to-point data transfer capability between SER-CAT and its member institutions. A similar network, called the South Carolina Light Rail (SCLR), is planned for South Carolina to connect the three major research institutions, MUSC, USC and Clemson.   “The only negative to emerge during the inaugural test of the system was the slowness of the existing network,” said Davies. “The SCLR connection to MUSC cannot come soon enough.”   Both the SCLR and Southern Light Rail are branches of the National Lambda Network, a national high-speed network dedicated to research and clinical support. MUSC’s connectivity with the SCLR system will have the capability of sharing and transferring data using a high-speed connection of about 10-gigabyte/second. For example, a 3-gigabyte brain scan that takes about 9.5 minutes to transmit using today’s capabilities can be transferred in just 3 seconds using SCLR.   “The South Carolina Light Rail connectivity and mechanism will be a key component in the next phase of growth for research and the university,” said Steve Lanier, Ph.D., associate provost for research.        An important outgrowth of this increased activity in crystallography at MUSC is the addition of a second crystallographer, Jeffrey Hansen, Ph.D., assistant professor, Department of Biochemistry and Molecular Biology. The effort also coincides with a major expansion in structural biology at MUSC in the field of NMR, culminating in the recent appointment of Mirko Hennig, Ph.D., assistant professor of Biochemistry and Molecular Biology, and the development of two new NMR facilities: one at the Hollings Marine Lab at Fort Johnson and the other in the Basic Sciences building at MUSC. Alongside efforts to increase capabilities in protein production to support both crystallography and NMR, the team’s present goal is to provide a world-class, integrated structural biology core situated in the campus’ planned Drug Discovery Building.      “In these activities, we are eager to place MUSC in the top tier of academic medical centers where investigators drive new knowledge, and knowledge-based clinical medicine and therapeutics,” Hannun said. “Structural biology would form the foundation of such a process that should extend to the clinic and beyond.” SCLR to connect research, patient care nationally, worldwide Bringing this level of technology to MUSC creates a limitless potential for scientists, researchers and clinicians to conduct collaborative medical research, advance patient care and enhance telecommunications on campus.      The S.C. Light Rail is part of a planned statewide super high-speed broadband network that will provide a fiber optic pathway and exclusive link to the state’s major scientific research institutions, Clemson, the University of South Carolina and MUSC, as well as connect the health partners of the state under the Health Sciences South Carolina collaborative. Providing this level of high bandwidth connectivity will allow scientists to conduct more real-time data analysis and research, enhance telemedicine and distance learning, plus support collaborative teaching.   Regionally, the light rail networks have already been established in Florida, Georgia, North Carolina and most recently, Alabama. These state networks were created to connect higher education institutions, government scientific facilities and research centers to each other as well as nationally through the National Lambda Rail connection.   “South Carolina needs this level of super high-speed connectivity,” said Roger Poston, Ph.D., associate professor and director for Academic and Research Computing, Office of the Chief Information Officer. “The Light Rail is a tool that would help us move in a direction that keeps us in pace with our goal for enhancing research growth and hopefully raise us to the top quartile among other national research institutions.”   Establishing this advanced high-speed network service and providing a basic infrastructure or foundation is essential to institutions and researchers who compete for and maintain federal grant money and extramural funding.   “This network is very important for MUSC and our state. If we don’t have it, we won’t receive or maintain funding for federal grants and other available research funding,” Poston said. “South Carolina won’t be competitive with surrounding states in areas such as biomedical research, patient care and telecommunications.”     Friday, March 9, 2007 Catalyst Online is published weekly, updated as needed and improved from time to time by the MUSC Office of Public Relations for the faculty, employees and students of the Medical University of South Carolina. Catalyst Online editor, Kim Draughn, can be reached at 792-4107 or by email, catalyst@musc.edu. Editorial copy can be submitted to Catalyst Online and to The Catalyst in print by fax, 792-6723, or by email to catalyst@musc.edu. To place an ad in The Catalyst hardcopy, call Island Publications at 849-1778, ext. 201.