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All the World's a Stage

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05/22/15 | All the World's a Stage

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Marta Zlatic photography by Eli Meir Kaplan
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Marta Zlatic is as capable of portraying the Greek heroine Hecuba as she is of pulling back the curtain on the neural circuitry of fruit fly larvae. At both pursuits, she's won wide acclaim.

It’s hard to imagine two settings more dissimilar than the vast rotunda of a Greek theater and a small, windowless microscopy room at HHMI’s Janelia Research Campus. But Group Leader Marta Zlatic is equally at home in both spaces. At this moment, her microscope’s narrow beam is illuminating a Drosophila fruit fly larva on its own stage, the semitransparent creature wriggling in a way barely perceptible to the naked eye. To Zlatic, the larva’s movements represent a nuanced performance fine-tuned by millions of years of evolution – and a foundation for understanding the neural basis of behavior.

Fifteen years ago, while she was an undergraduate at the University of Cambridge in England, Zlatic herself was in a spotlight onstage – as Hecuba, the ill-fated queen in the Euripides tragedy,The Trojan Women. A student of linguistics and neuroscience, Zlatic knew ancient Greek and had attended the audition for the play out of curiosity. Lacking acting experience, she was assigned a role in the chorus. When the lead actress quit halfway through rehearsals, however, the director, impressed by Zlatic’s fluency with the language and text, asked her to step in. Audiences and critics cheered the performance, and Zlatic went on to land a string of roles known for their complexity: Electra, Medea, Lady Macbeth, even Oedipus Rex.

“Anyone who has seen a play should wonder: How can this wonderful system, the brain, produce so many different emotions and behaviors?” Zlatic says today, seated in her sparsely decorated office upstairs from the microscope room in Janelia’s east wing. Three empty champagne bottles, one for each major paper published by her lab in its five years of existence, sit next to her computer. The bottles, along with the humble model organism she has chosen as her life’s work, make a quiet statement about the patience required of scientists who study such ambitious questions. To go big, you must often start small.

Zlatic leans forward. The human brain, she explains, has 100 billion neurons, roughly equivalent to the number of stars in the Milky Way. Fruit flies have only 100,000, and a fruit fly larva just 10,000. Reduce a nervous system to that relative simplicity, and suddenly it becomes possible to study it comprehensively – not only to describe what it looks like (map it visually), but also to determine which cells connect to one another (map its wiring, or “connectome”) and to figure out how those networks listen and respond to signals from the outside world (map its behavior). Zlatic’s team, with a constellation of collaborators at Janelia and around the world, is building something akin to Google Maps for the larval brain, placing these layers of information on top of each other like satellite images overlaid on roadways. They are now beginning to outline, with neuron-by-neuron precision, the neural circuits that determine how a larva responds to its environment and decides what actions to take.

Read the rest of the story in the HHMI Bulletin.