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First-year graduate students Chang, 25, and Anni Zhao, 23, who recently joined the Eisenberg lab, started with little knowledge of the field. The learning curve was steep, but both were impressed by the instructors' creativity and skill in conveying the needed information. For example, to appreciate the various kinds of symmetry crystals can adopt, students begin by identifying symmetrical elements in the mathematically inspired artwork of M.C. Escher.
In the sequence of instruction, the first part explains x-ray crystallography as well as nuclear magnetic resonance (NMR) and electron microscopy—techniques that can be applied to atomic structure. “We teach them how to read a paper, how to know if a structure is reliable, and what assumptions have been made,” Eisenberg says.
Next come two five-week segments delving deeper into the actual mechanics of x-ray and NMR crystallography—collecting and reducing data and then determining the structure from the data. Along with the lectures, students practice what they've been learning with a set of laboratory problems. “Because it's such a complex concept to teach, it really helps that Dr. Eisenberg is able to bring in six instructors who specialize in different areas,” says Zhao.
Finally, it's time to put it all together: the students are given a protein from which to grow crystals, freeze them, mount them in the x-ray apparatus, gather the data, and interpret the structure. “To get a good crystal that gives you a nice diffraction pattern is a big deal,” says Zhao. “The initial formation is difficult: there are many combinations of factors—concentration, pH, temperature, salts, buffers—and the possibilities go up exponentially.”
Zhao praises Eisenberg for his supportiveness in helping students weather the ups and downs. “He does not push you for results, but when you need direction or help, he is always available and extremely helpful,” she says. “People can go into his office very frustrated and walk out the door more motivated than ever.”
In practice, much of the tedious trial-and-error pipetting is now done with automated equipment, Eisenberg says, but going through the process manually is part of the learning experience. After completing the course, students are well prepared to join a lab group that relies on x-ray crystallography for structure analysis.
“Some of our students go on to become real experts in the field—they far surpass me in mastering the software and the hardware,” he says. “Others just use it for their research as biochemists. What I like about our training system is that it provides a basis for both of those careers.”