New directions for UB’s BioXFEL

When the National Science Foundation awarded $25 million to UB and its partners in 2013 to establish an X-ray laser science center, a primary goal was to study biological processes. While traditional X-ray crystallography has been providing static pictures of proteins for a hundred years, the new center, called BioXFEL, was created to bring those pictures to life, making movies of proteins and other biologically important molecules.

“The goal is to reveal the dynamic stories behind basic biology,” says Eaton E. Lattman, BioXFEL director and professor in the UB Department of Structural Biology, Jacobs School of Medicine and Biomedical Sciences, and in the Department of Materials Design and Innovation (MDI), School of Engineering and Applied Sciences. Lattman also is former chief executive officer of the Hauptman-Woodward Medical Research Institute (HWI).

Since the award, BioXFEL researchers in Buffalo and at its partner institutions around the world have made significant progress in refining X-ray laser techniques to study biological processes. 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.

But UB’s experience is proving that the power of X-ray laser science can reap benefits for non-biological disciplines, as well as for those that are biological.

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,” Lattman says.

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,” he 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,” Lattman explains, “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.”

That versatility excites Krishna Rajan, the Erich Bloch Endowed Chair in UB’s new Department of Materials Design and Innovation (MDI), a partnership between the School of Engineering and Applied Sciences and the College of Arts and Sciences.

When Rajan arrived at UB from Iowa State University in 2015 to start the new department, BioXFEL was a big attraction. “BioXFEL is a huge asset that has become a major part of my strategy for growth in MDI,” he says. “We got involved with BioXFEL almost immediately.”

According to Rajan, the fundamental issues in protein crystallography are at the nexus of biology and materials science, or as he puts it: “It’s all about molecules.” He describes materials science as a field focused on linking how the behavior of molecules and atoms scales up to influence the behavior of materials.

“The field of crystallography is core to advancing this understanding,” he explains, “whether it be protein molecules or complex alloys and ceramics. Aside from the commonalities of crystallography, the field of ‘soft matter’ is a core sub-discipline in materials science and hence fits well into the research areas of MDI.

“The BioXFEL program offers a unique opportunity to develop new ways to probe matter at the scale that underlies the future of the design and discovery of materials; hence, the study of molecular motion has impact in a broad range of technological applications,” Rajan says, adding that the new MDI department is unique in advancing structural biology as part of its portfolio in soft matter.  

In addition, he notes, X-ray laser science is a tremendously data-intensive technique, generating massive amounts of data that help drive new discoveries. “A key distinguishing feature of the department I’ve started here is, coincidentally, that it’s built around the idea of data-intensive research. We’ve taken the view that data science itself is part of the subject matter.”

Having unrestricted access to those data is a powerful benefit, Rajan says. “BioXFEL gives us a big leg up. We can be part of BioXFEL’s online systems, giving us tremendous access both to data and to the people who generate those data so we can collaborate with them. Having BioXFEL here allows us to be part of that community. It’s tremendous,” he says.

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 “go-to” conference 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.

BioXFEL also has developed an innovative partnership with the University of Puerto Rico, (UPR), holding customized workshops at UPR 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.”

Rodriguez Perez says she wants to keep working in crystallography incorporating the XFEL research.

Gabriela Casanova Sepulveda, an undergraduate at UPR, has participated in two BioXFEL internships, learning all about structural biology, from protein expression and purification to crystallography and X-ray experiments. “The best part about my internships has been my exposure to a world of really interesting science,” she says. “I have learned many techniques that have helped me become a better scientist, from how to express a protein to how to make a good scientific poster.

“What I’ve also loved about this program is that they keep in touch with you to know if you, as a student, have met your goals or if you are on the right path,” she says. “I’m actually thinking of applying for graduate school in a structural biology or biophysics program. BioXFEL has been determinant in helping me meet my future goals.”

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; and Lawrence Berkeley National Laboratory.