Undergrad Helps Find Lethal Gene

Joshua R. Wortzel ’13 has always been fascinated by genetics: as a young boy he discussed evolution with his father from the bathtub, and in 6th grade he bred 70 mice in his basement while conducting a Mendelian-inspired experiment on coat color.

Now a researcher at Harvard Medical School Professor Christopher A. Walsh’s neurogenetics lab, Wortzel is exploring his passion once again.

Last summer, he joined a project working to identify a gene whose mutation causes microcephaly, a typically lethal condition characterized by abnormally tiny brains. Microcephaly often results when progenitor cells—the “stem cells” of the brain—die prematurely or differentiate too quickly to form a whole brain.

After sampling DNA from eight children in a Palestinian Arab family—seven of whom had the neurodevelopmental disorder microcephaly—researchers at the Walsh lab were able to isolate one gene that was commonly mutated among all of the afflicted children.

The researchers observed that a similar copy of the gene is located on the mouse genome. By mutating that gene in mice, Wortzel and his colleagues have been able to confirm that mutations of the gene in question (whose name Wortzel cannot reveal until it is officially published) result in altered progenitor cells, strengthening evidence that the gene may be responsible for microcephaly.

“I think it’s pretty cool that you’re faced with a mystery, and in a very systematic way you can go about peeling that mystery,” he said. “It’s a puzzle—a creative outlet.”

This enthusiasm is one of the most important traits an undergraduate can bring to the laboratory, said Walsh, Wortzel’s research adviser.

“He’s really, really smart, and that’s the most important thing. But you know that is not the only important thing for being a good researcher,” said Waslh. “First of all, you have to be an optimist. You always have to be skillful with your hands. And then you have to be fearless.”

The human developmental and regenerative biology concentrator has begun independent research on the function of the gene that Wortzel and his colleagues believe may be behind microcephaly. Wortzel said that recent research suggests that it influences the modification of histones, which play an important role in gene regulation.

Flourescently tagged antibodies only stick to histones with certain residues. By inserting these antibodies into cells from human control and mutated samples, Wortzel can identify whether the gene mutation affects histone modification.

Wortzel said his interest in neurobiology and genetics is in large part due to personal experience—his grandfather suffered from Alzheimer’s and in middle school Wortzel was “big brother” to a boy with autism.

“The brain makes us human, but when it goes wrong there’s little we can do about it,” he said.

—Staff writer Radhika Jain can be reached at radhikajain@college.harvard.edu.

This article has been revised to reflect the following correction.

CORRECTION: Feb. 13, 2011.

The Feb. 4 article "Undergrad Helps Find Lethal Gene" misstated the middle initial of Harvard Professor Chistopher A. Walsh.