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The Order of the Flies
Brain Detectives
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Front Lines
Research Notes
Notable Results
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Brain Detectives
Husband-and-wife neuroscientists Gina Turrigiano and Sacha Nelson are unlocking the secrets of the brain
Illustration by Amy Patacchiola
By Michael Blanding
Imagine your brain as a maze of connecting doors, each one opening only to a specific key. In a healthy brain, messengers unlock doors in rapid succession, traveling speedily to deliver orders—whether to move a limb or register the sight of a cat.
In a dysfunctional brain, however, keys are broken or missing, or replaced by forgeries. Would-be couriers get stuck, knocking on locked doors in vain or opening wrong doors and wandering far afield.
That analogy is at the heart of research being done by biology professors Gina Turrigiano and Sacha Nelson. Their work describing brain circuitry has changed the way scientists think about how the brain is wired, and someday it may unlock the secrets behind intractable developmental disorders like autism.
“All of our cognitive abilities come from the right cell types connecting to the other right cell types with a sort of lock-and-key mechanism,” says Turrigiano. “We ask how the process of forming these connections goes awry.”
The two are not only partners in science but also husband and wife, referring to their labs as “Neliano”—a combination of their last names—and collaborating as much over the dinner table as over the petri dish. Sharing a sardonic sense of humor and a clear affection for each other, they finish each other’s sentences and chide each other on areas of minor disagreement.
Together, they focus their research on Rett syndrome, a rare disease in which young girls develop normally for several years but then lose their ability to walk or talk, eventually deteriorating into an impassive state. Caused by a malformation of a single gene, Rett syndrome is comparatively easy to isolate and model in the lab.
“We understand the biology of Rett’s, so we can reproduce it in the mouse,” says Nelson, who talks in a slow, deep voice in contrast to the rapid-fire articulations of his wife. Because Rett syndrome has similarities to autism, however, many of the discoveries they are making could one day be vital in understanding that condition as well.
Located across the hall from each other, the Nelson and Turrigiano labs roughly break down along “nature-versus-nurture” lines. Nelson’s lab studies the genetic makeup of the brain—no small order, when you consider that the brain is made up of 10,000 different cell types and that problems with any one of them could change the keys the cells need to communicate effectively.
Turrigiano, meanwhile, exposes neuronal cells to different stimuli to see how they develop in response to their environment. Amid the clutter of wires and beakers in Turrigiano’s lab is a shiny metal slicer not unlike those at the deli meat counter—except this one slices mouse brains to the width of three-tenths of a millimeter. As if they were in the lab of a mad scientist from a 1950s horror movie, the brain slices are kept alive in a small dish of bubbling cerebral fluid. Graduate students place slices under a microscope attached to cameras and fire individual synapses with glass pipettes, recording how they develop over time.
“You really can watch the living neurons growing and retracting,” says Turrigiano. “It’s pretty wild!”
Working between the two labs, the scientists compare the brain cells of normal mice with the cells of mice that have the Rett mutation in an effort to determine how the circuitry gets miswired.
Turrigiano and Nelson met and fell in love as doctoral students at the University of California, San Diego. “It’s the juicy part of the story, but we’d prefer not too much of this story be about that,” warns Nelson, before Turrigiano cuts in: “He was engaged to someone else before he came to his senses and realized I was the woman of his dreams.”
“That’s exactly the kind of thing I didn’t want to get into,” deadpans Nelson.
Facing the difficulty of finding two faculty positions in the same city, the two initially accepted an unusual joint position in
Brandeis’s biology department in 1994; it was later expanded to two full-time positions. The dual position had the positive side effect of causing them to collaborate more closely than ever before.
Turrigiano first studied individual brain cells, while Nelson looked at larger cortical circuits. In part, it was their young children who caused Turrigiano to change her focus to brain development.
“Before I had kids, I was interested in what the brain did in its fully developed state. Then you watch this incredible process of your kids interacting with the world and adapting to it, and understanding how this happens seems like the most fascinating problem of all,” she says.
Seven years ago, Turrigiano received a $500,000 MacArthur “genius” grant for her groundbreaking work in how the brain regulates synaptic connections so they don’t “overexcite” themselves in response to stimuli. At the same time, the progress of the Human Genome Project and emerging new techniques for measuring gene expression fascinated Nelson, who began to look at the brain on the cellular level. He is now pursuing the ambitious goal of cataloging all of the thousands of different cell types in the brain into a map he calls the “neurome.” When completed, it could revolutionize neurology in the same way that mapping the human genome revolutionized genetics.
The two labs also collaborate on methodology. Nelson has adopted Turrigiano’s techniques to study cells, while Turrigiano uses Nelson’s process of slicing mouse brains. That kind of sharing is a hallmark of Brandeis science, say the two scientists, who expect the new Shapiro Science Center to promote even more faculty collaboration.
“Just having space where you can sit down and have coffee with a colleague or student, along with a white board to illustrate your ideas, only will intensify an already really great feature of Brandeis,” says Turrigiano.
“When some of the present buildings were built in the fifties and sixties, Brandeis was an amazing powerhouse for a university so new and so small,” says Nelson. “The buildings represented a commitment to growth in the sciences, and that continues to be true.”
No doubt the new building will continue to unlock doors of discovery.