NSF extends BioXFEL Center mission to image motions of molecules

Rice biochemist George Phillips leads internship training as well as new paths to discovery via X-ray lasers

Rice University biochemist George Phillips and his lab are celebrating the continuation of a National Science Foundation (NSF) grant to extend the BioXFEL Science and Technology Center.

The center, based at the University at Buffalo, won the $22.5 million grant to continue its groundbreaking development of advanced imaging for critical biological processes that are often impossible to see with conventional methods.

The work aims to enhance drug development, better understand biological processes and lead to potential innovations in environmental technologies and materials.

Rice scientists and colleagues at Stanford, Cornell and Arizona State universities, the University of Wisconsin-Milwaukee, Miami University in Ohio and the University of California, San Francisco have already employed the center’s X-ray laser resources to analyze ever smaller structures in greater detail.

Rice hosted summer interns this year as part of its commitment to the BioXFEL Center, which is developing advanced X-ray crystallography imaging for critical biological processes. Members of this year’s cohort, from left: Rice graduate student Abigael Kosgei, German Banda, Megan Vu, Courage Owhonda, Esther Jimenez, Professor George Phillips, Carlos Reyes-Leon, Alyssa Alvarez, Chiagoziem Ngwadom, Tasmia Nadeem, Sarah Bradford, Haania Kakwan and graduate student Joey Olmos. Courtesy of the Phillips Lab

The data they gather through X-ray laser crystallography helps them understand such biological phenomenon as how drugs bind to targets and how photosynthetic bacteria find light. Earlier this year, Phillips and Rice graduate student Jose Olmos led a study that showed how drug-resistant tuberculosis bacteria deactivate the antibiotic molecules intended to treat the disease.

Phillips said Rice postdoctoral researcher Jonathan Clinger, who earned his Ph.D. at Rice, used BioXFEL to complete work on light-signaling phytochromes reported in a Nature Methods paper last year. Rice research scientist Mitch Miller contributes to data analysis and was co-author of the phytochrome paper and a 2016 paper on XFEL enzymology.

The Rice researchers and their colleagues used the X-ray free-electron laser at the Department of Energy’s SLAC National Accelerator Laboratory at Stanford. The mile-long facility produces intense X-rays one-tenth the thickness of a human hair in pulses as short as 20 femtoseconds (quadrillionths of a second).

“In the next five years we expect to move beyond our initial technology development to study the dynamics of molecules,” said Phillips, Rice’s Ralph and Dorothy Looney Professor of Biochemistry and Cell Biology. “The basic understanding we stand to gain will teach us more about how nature selects for and designs molecules to work.

“Any time you want to engineer a protein or recreate a molecular machine, knowing more about how it works at a fundamental level is going to be helpful, whether it’s breaking down cellulose for biofuels or designing a new drug or improving an existing drug,” Phillips said.

Venu Govindaraju, vice president for research and economic development at Buffalo, said XFEL scientists have discovered about 350 new molecular structures and produced more than 500 publications. “With these incredibly powerful new tools, they are helping us better understand some of society’s most intractable health and science problems,” he said.

The XFEL gathers data from streams of folded, crystallized proteins that flow into the path of the laser. When hit by the pulse, they are quickly destroyed, but not before the XFEL captures an image of their atomic arrangement. Researchers use computers to analyze the images from a single stream to determine the protein’s crystal structure. “What we get is a final structure that’s the average of a million or so single-particle shots,” Phillips said.

He noted that while the Stanford facility will shut down for an upgrade in 2019, other XFEL facilities are coming online in Europe, Korea, China and Japan. More powerful devices will get scientists closer to their immediate goal of imaging entire, non-crystallized molecules that now disintegrate too quickly for imaging.

“Hopefully by the end of the second five-year period we can say our center made a significant contribution to single-particle imaging,” Phillips said.

One of the center’s objectives is training young scientists for XFEL careers, including summer intern programs, graduate student support and postdoctoral career-development activities.

“I’m particularly proud of not only the research but the summer internship program, in which we bring 10 mostly underrepresented kids to Rice to work on research related to this, and then they get to go visit the big laser at Stanford in the fall,” said Phillips, who serves as director of education and diversity for the BioXFEL Center.

“It’s operated as a supplement to the main center grant, but this is the third year we’ve hosted the program,” Phillips said. “It’s a year-to-year supplement, but the NSF seems to appreciate it. During our formal site visit, they gave us high marks for our outreach efforts.”

Olmos, who helps coordinate the summer program, noted that two of this year’s 10 interns took home poster presentation awards at the annual undergraduate research symposium hosted by the Institute of Bioscience and Bioengineering. “(We’re) already missing their energy and enthusiasm,” he tweeted.

Details about the internship program are available at https://ibb.rice.edu/bioxfel-internship.