$25 million grant will help support x-ray laser imaging of biomolecules

The National Science Foundation (NSF; Arlington, VA) has awarded the University at Buffalo (UB; Buffalo, NY) a $25 million grant to transform the field of structural biology, including drug development, using x-ray lasers.

With the grant, UB and its partner institutions will establish the BioXFEL research center in Buffalo, which will focus on developing new x-ray bioimaging techniques. One technique involves an advanced form of x-ray crystallography called serial femtosecond crystallography to analyze an array of new molecular targets for drug discovery. The technique will provide scientists with new insights into how biological molecules function, what might be happening when disease occurs, and what compounds might be designed as drugs to modify this activity.

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While current techniques in crystallography provide almost 90 percent of what scientists know about biomolecular structure, fewer than 20 percent of purified proteins currently form the crystals necessary for this technique.

“We will be able to analyze crystals 1,000 times smaller than the ones we can use now,” says Eaton E. Lattman, Ph.D., professor in the UB Department of Structural Biology in the School of Medicine and Biomedical Sciences and CEO of the Hauptman-Woodward Medical Research Institute (HWI), who will serve as the director of the BioXFEL center. “These are crystals we could never use before and, in fact, may not have known existed. A whole new universe of drug targets will become accessible for study as a result.”

John C.H. Spence, Ph.D., Regents’ Professor of Physics at Arizona State University (ASU; Phoenix, AZ), who will serve as the center’s scientific director, notes that the research team will also be developing new techniques for making movies of molecular machines at work, and of viruses and biomolecules in their natural wet environment undergoing chemical change. "Some of the work, with Prof. Petra Fromme at ASU, will try to image the detailed atomic processes responsible for photosynthesis," he explains.

“The techniques the BioXFEL center will develop could shorten the process of determining protein structure from years to days,” says Abbas Ourmazd, Ph.D., Distinguished Professor of Physics and Electrical Engineering at the University of Wisconsin-Milwaukee (UWM), which will have a primary role in the center. “This will rely heavily on mathematical algorithms we and others are developing to deduce structure from millions of ultralow-signal snapshots.”

Scientists involved with the BioXFEL center will use an extremely powerful new kind of x-ray beam developed at SLAC National Laboratory at Stanford University called an x-ray free-electron laser (XFEL). "The XFEL beam is unbelievably intense and is composed of a sequence of unimaginably short pulses that act like flashbulbs to freeze the motions of protein molecules when the beam zaps them," explains Lattman. “In the long run, the x-ray laser will allow us to make movies of molecules, rather than having to infer their motions from fixed pictures."

ASU will be a major research partner, providing expertise through Spence’s lab, which specializes in determining the structures of membrane proteins and viruses, which are difficult to crystallize. UWM will provide key theoretical and experimental contributions.

The center will emphasize applications of its research through its industrial partners in the Industrial Macromolecular Crystallography Association comprised of major pharmaceutical companies, including Bristol-Myers Squibb, Pfizer, Abbott, Merck, and Novartis.

For more information, please view http://youtu.be/VQpqI5eNEJU.

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