SEPTEMBER FEATURE
Crystal Clear: What is X-Ray Crystallography?
Proteins are critical to the survival of every living thing on the planet. From storing energy to digesting the food we eat, proteins carry out a multitude of functions in cells, and their importance cannot be overstated. But individual proteins molecules can’t be seen with the naked eye, or even with a microscope. Instead, scientists must use different techniques to determine the structure and function of specific proteins.
X-ray crystallography is one technique that scientists frequently use to “see” proteins. Unlike light, which passes right through proteins, X-rays are deflected when they hit a protein. Scientists can then study the direction that an X-ray bounces to determine the shape of what it hit. But because a single protein is far too small to provide an accurate reading, they use a crystal to amplify the signal.
Imagine you’re standing on the top of a mountain and someone is shouting at you from the bottom. You’re not going to be able to hear the person. But what if, instead, 10,000 people are at the bottom of the mountain, all facing in the same direction and shouting the same thing at the same time? Their combined voices will create a much stronger sound.
It’s the same with crystallography. Scientists entice a large number of proteins to form crystals, essentially locking them all in the same orientation. Then, when that crystal is hit with X-rays from enough different directions, the resulting data can be mathematically transformed from a string of numbers into a complete, three-dimensional snapshot of the protein.
Image of protein crystal.
It can safely be said that Madison-based biotech firm Bruker AXS—as one of only two companies in the world that manufactures analytical X-ray systems—is at the forefront of its field.
But even big companies sometimes need a hand. And when Bruker needs someone to test its latest innovation or write complementary software to increase the functionality of its hardware, the company knows the person to ask: George Phillips.
UW-Madison professor of biochemistry and computer science George Phillips (right) and scientist Craig Bingman assess the Crystal Farm, an automated crystal growing and screening system at UW-Madison’s Center for Eukaryotic Structural Genomics. Photo: Jim Gill
Phillips, a UW–Madison professor of biochemistry and computer science, is one of the principal investigators of the university’s Center for Eukaryotic Structural Genomics, which conducts research on the structure of proteins (see sidebar). Through a partnership with Bruker, which designs and builds equipment used in such research, Phillips and the center now help test and develop new tools to enhance Bruker’s product line.
“Bruker is a world-leading supplier of equipment required to solve protein structures. So when [the center] needed some equipment, we partnered with Bruker with the understanding that we would be a demonstration site for them,” says Phillips.
The arrangement has benefited both parties. Bruker, with global operations valued at more than $200 million, obviously does its job well, but the company can’t always put its equipment through the paces as customers do, says Dan Frankel, manager of Bruker’s life sciences division in the company’s Madison office.
“We build the equipment, but we don’t do our own research, which makes it very difficult [for us] to test the equipment,” he explains.
Phillips’ group possesses an array of talents that makes their services uniquely desirable to a company like Bruker.
“There are about seven or eight [laboratory] groups in the country that do what [Phillips and the center] do,” says Frankel. “The fact that George’s lab is just across town has been great for us.”
Frankel cites Phillips’ and scientist Craig Bingman’s contributions to enhancing the utility of the Crystal Farm, Bruker’s automated crystal-growing-and-screening system. Phillips’ team, which includes several UW undergraduates, wrote a software program, called Crystal Farm PRO, that automatically calculates screens to identify the conditions where a protein will crystallize, a time-consuming process that used to be done manually by the scientist. With the new software, all the scientist has to do is provide the previously identified conditions and specify the desired range to be screened.
Dan Frankel, manager of the sciences division of Bruker AXS, stands outside the company’s Fitchburg manufacturing warehouse. “He [Phillips] had a need for the functionality of software, and I needed his brains,” says Frankel of his partnership with UW-Madison’s Center for Eukaryotic Structural Genomics. Photo: Jim Gill
“He had a need [in his lab] for the functionality of that software, and I needed his brains,” says Frankel.
The program was originally designed as an add-on to the software package already offered with the Crystal Farm, but according to Frankel, it may soon become part of the standard package. “The market is moving toward more automation, and pretty soon we won’t be able to sell [Crystal Farms] without it,” says Frankel. “I expect to sell it to most of my installed base, as well.”
While the current phase of software development has been completed, both parties are looking forward to future collaborations.
“We’re really interested in sharing our knowledge of the equipment with the scientific community. We hope the relationship continues so we can write more [software] to make things easier for us and other labs,” says Phillips.
Frankel is equally enthusiastic about future work with the center.
“We love them,” he says. “It’s just a fantastic relationship for us.”
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