UB Receives $25 Million to Develop New X-Ray Bioimaging Technique

With this Science and Technology Center (STC) grant, UB and its partner institutions will establish the BioXFEL research center, headquartered in Buffalo.

The center will focus on developing new X-ray bioimaging techniques — including an advanced form of X-ray crystallography called serial femtosecond crystallography — to analyze a vast array of new molecular targets for drug discovery.  

This technique has the potential to spur innovation in the pharmaceutical field. It will provide scientists with insights into how biological molecules function, what might happen when disease occurs and what compounds might be designed as drugs to modify this activity.

“With this prestigious award, the University at Buffalo deepens its national leadership and long tradition of groundbreaking health research and the innovative treatment of disease,” says SUNY Chancellor Nancy L. Zimpher.

Tim Killeen, PhD, SUNY’s vice chancellor for research, says the “cutting-edge research will showcase UB’s stature as a world-class research university.”

Killeen, who also is president of the Research Foundation for SUNY, calls the grant the “premier award given out by NSF.”

“NSF selects just a handful of STC winners every four years from a pool of hundreds of applicants,” says UB President Satish K. Tripathi.

This is the first STC grant UB has received.

The establishment of the BioXFEL center will put the university and Western New York in the forefront of the new X-ray imaging technology, says Alexander N. Cartwright, PhD, vice president for research and economic development at UB.

“It has the potential to transform the way scientists study diseases and develop new treatments,” he says.

Tripathi notes that the center’s research will build on the region’s “rich legacy of expertise” in X-ray crystallography, historically based within the Hauptman-Woodward Medical Research Institute (HWI), which is UB’s Department of Structural Biology.

Eaton E. Lattman, PhD, professor of structural biology and chief executive officer of the HWI, will direct the center. In a video interview, he explains the center’s research objectives and potential impact.  

HWI expertise will play a central role in the new center. Its National Institutes of Health-funded high-throughput screening laboratory has been growing crystals of proteins for hundreds of client labs throughout the United States for a decade.

The center will be located at the HWI, on the Buffalo Niagara Medical Campus.

Lattman says the new bioimaging technique that will be developed in the BioXFEL center will enable scientists to analyze crystals 1,000 times smaller than the ones they currently use. 

“These are crystals we could never use before and, in fact, may not have known existed,” he says. “A whole new universe of drug targets will become accessible for study as a result.”

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

Lattman notes that the new technique offers tantalizing possibilities in the future.

“Maybe down the road, we won’t even use crystals at all, but we’re a long way away from that,” he said. 

Scientists involved with the BioXFEL center will use an X-ray, free-electron laser (XFEL) — an extremely powerful new kind of X-ray beam — that will let scientists see the motions of molecules for the first time. 

Lattman says he hopes the center will create the resources and knowledge that allow scientists to apply XFEL routinely to the most pressing biomedical questions within five years.

He explains that the XFEL beam is “unbelievably intense” and is composed of a sequence of short pulses that act like flashbulbs to freeze the motions of protein molecules when the beam zaps them. 

“Most biological processes require movements within the molecules involved, but the pictures provided by current X-ray analysis contain very limited information about them,” says 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.”

The use of the XFEL to analyze proteins crystals was chosen by the journal Science as one of the top 10 science breakthroughs of 2012; that work included a number of scientists who will participate in the BioXFEL center.

UB will be one of the key institutions in the nation developing young scholars in this technique, says Lattman.

Along with two of its partner universities — the University of Wisconsin-Milwaukee (UWM) and Arizona State University (ASU) — UB will offer educational programs at the graduate, postdoctorate, undergraduate and high school levels.

The BioXFEL educational program will be directed by Margarita L. Dubocovich, PhD, chair of pharmacology and toxicology and senior associate dean for inclusion and cultural enhancement.

John C.H. Spence, PhD, Regents’ Professor of physics at ASU, will be the center’s scientific director. His lab specializes in determining the structures of membrane proteins and viruses, which are difficult to crystallize. 

UWM, led by principal investigator Abbas Ourmazd, PhD, Distinguished Professor of physics and electrical engineering, will provide key theoretical and experimental contributions.

Other partner institutions are Cornell University, Rice University, the University of California at San Francisco and Stanford University. Contributors at the University of California at Davis will help create and manage the educational program.