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Their success fueled Jinks’ bold and risky idea: to restructure his neurochemistry course to support the clinic team’s genetic discoveries. “It was probably ambition coming off a really exciting sabbatical,” he says. “But it is a very unique population of patients and a great group of students.”
Mutations and Behavior Changes
Jinks went forward with the restructured course, teaching undergraduates how to make strong connections between the bedside and bench. Some students did so literally, by going to the clinic to meet patients and taking that experience back to the lab. Independent study student Rebecca Willert, for example, studied a Mennonite family in which five members displayed a form of intellectual disability characterized by learning delays. Through gene mapping and sequencing of family members’ genomes, the clinic team had come up with a single gene as the possible culprit. Puffenberger handed over that information to Willert, in addition to—with the patients’ consent—medical records data detailing symptoms and onset.
By searching bioinformatic databases, Willert hypothesized that the normal gene, called CRADD, regulates how brain cells sprout and maintain proper connections. Her cellular studies showed that the mutated version of CRADD found in the Mennonite family alters the ability of the CRADD protein to interact with other proteins necessary to initiate programmed cell death. Thus, her findings offered a potential reason for the patients’ cognitive and learning deficits.
"The critical thinking involved, thinking of these things as puzzles, has been captivating."
With Strauss and team, Willert shared her scientific sleuthing story with the family and at the annual meeting of the Society for Neuroscience in Washington, D.C., in November 2011.
“We were looking for answers to whatever would cause this,” says family member Geneva Martin, whose three sons, brother-in-law, and sister-in-law are affected. “It helps just to know.”
Willert says that meeting the family helped her gain a better focus in the lab. “I could put a name and face on what I had been studying for so long,” she says, “and actually see the kids and how they interacted.”
Now she can imagine how a mutation in a nerve cell might translate into the behavioral changes that she saw. It also helped her better design the experiments that she conducted this past summer when she was hired by the clinic team to continue her work.
Shaking off those first-day jitters, Achilly took to the project as well. After two years uncovering how a mutation in an enzyme involved in protein synthesis might cause Usher syndrome type IIIB, characterized by hearing loss and progressive vision loss, Achilly, who graduated in May, has expanded his sights beyond a medical degree. He now plans to pursue an M.D.,Ph.D. in translational neuroscience.
“The two years of experience that I gained from Rob’s lab have changed my life in many ways,” he says. “The critical thinking involved, thinking of these things as puzzles, has been captivating.”