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Research Center Taking X-ray Laser Science in New Directions

Published April 27, 2017

Eaton E. Lattman, PhD

Eaton E. Lattman, PhD

Researchers at the BioXFEL Science and Technology Center in Buffalo and at its partner institutions around the world continue to make significant progress in refining X-ray laser techniques to study biological processes.

“This is a powerful technique for identifying new drug targets. You’re no longer looking at a fixed target; instead, maybe there’s a whole spectrum of drug targets.”
Professor of structural biology

But the center, created in 2013 by a $25 million award from the National Science Foundation (NSF), is also proving that the power of X-ray laser science can reap benefits for non-biological disciplines.

Examining Biological Molecules in Atomic Detail

While traditional X-ray crystallography has been providing static pictures of proteins for more than 50 years, BioXFEL was created to bring those pictures to life, making movies of proteins and other biologically important molecules in atomic detail.

“The goal is to reveal the dynamic stories behind basic biology,” says Eaton E. Lattman, PhD, BioXFEL director and professor of structural biology and former executive director of the Hauptman-Woodward Medical Research Institute (HWI), where the center is headquartered.

The team at the University of Wisconsin-Milwaukee, for example, has used the technique to demonstrate the first step that occurs in vision, a small light-induced change in a protein that takes less than a millionth of a millionth of a second.

Powerful Technique for Identifying New Drug Targets

X-ray lasers, also called XFELS (for X-ray free-electron lasers), are superpowerful versions of the familiar laser pointer. They produce highly parallel beams in which the X-ray waves are perfectly superimposed.

The only place in the nation where such beams are available is at the Linac Coherent Light Source at BioXFEL partner Stanford University, where a mile-long facility produces an X-ray beam one-tenth of the thickness of a human hair. The beam is composed of a train of pulses so short they act like flashbulbs, freezing the motions of atoms and molecules so scientists can study every step.

“This is a powerful technique for identifying new drug targets,” says Lattman, who is also a professor of materials design and innovation in the School of Engineering and Applied Sciences.

Left: Experimental pattern produced by an X-ray laser beam bouncing off a crystal of the cathepsin protein from the parasite that causes African sleeping sickness. Cathepsin is a promising target for new drugs to treat this disorder. The subtle background between the spots adds important new information, and it could not have been seen without the X-ray laser.
Right: The pattern calculated from a model of the same crystal. The extraordinary similarity between the observed and calculated patterns, including the subtle variations in background, demonstrates that BioXFEL’s picture of the cathepsin protein is accurate and useful for drug design.

Solar Cells, Artificial Membranes Can Also Be Studied

While the lock-and-key metaphor is the conventional way of describing drugs binding to receptors, the understanding of how molecules move introduces a whole new way to devise potential treatments.

“Now you’re no longer looking at a fixed target; instead, maybe there’s a whole spectrum of drug targets,” Lattman says.

That kind of transformation isn’t just limited to biological applications.

“The same technology can be used to study all kinds of other things, such as solar cells, artificial membranes and innovative man-made materials, to find out what these things look like and how they move in functional cycles,” he explains.

BioXFEL Conference Has Become ‘Go-To’ Event

As an NSF science and technology center, a big part of BioXFEL’s mission is to cultivate a new, diverse population of young scientists who can use these pioneering X-ray laser techniques as they begin their scientific careers.

Toward that end, BioXFEL has begun holding an annual conference that has become the preeminent event in X-ray laser science, attracting more than 150 attendees every year.

The BioXFEL internship program began in 2014 with a dozen interns at UB and HWI, Rice University, Arizona State University and the University of Wisconsin-Milwaukee selected from a pool of 47 applicants. By 2016, the applicant pool had expanded to 214, with many being women or underrepresented minorities.

Innovative Partnership with University of Puerto Rico

BioXFEL also has developed an innovative partnership with the University of Puerto Rico (UPR), holding customized workshops and sponsoring a fellowship program for four UPR students, one of whom was given the opportunity to conduct experiments at the Stanford facility as part of her experience.

For UPR graduate student Josiris D. Rodriguez Perez, her internship with BioXFEL was a transformational experience.

“This internship was life-changing. I worked on a project related to my doctoral thesis,” she says. “I had wanted to find the structure of an unknown protein complex. During the internship, I could get crystals from the proteins, reproducibly and consistently. This was the critical part because before the internship, I couldn’t manage to get those precious crystals.”

UB Leads Consortium of Research Institutions

In addition to the institutions noted above, other BioXFEL partners are:

  • the Center for Free-Electron Laser Science in Germany
  • Cornell University
  • the University of Southern California
  • the University of California, San Francisco
  • the University of Pittsburgh
  • Lawrence Livermore National Laboratory
  • Lawrence Berkeley National Laboratory