Scientist tracks behavior’s neural roots in tiny brains

In 1848, an accidental explosion at a Vermont railway yard propelled an iron spike clean through the brain of a railway worker named Phineas Gage.

The spike severely damaged the left part of Gage’s brain. Not only did he survive, he escaped serious motor and speech problems too.

Gage’s personality, however, was altered by the accident, and he reportedly changed from a mild-mannered man into a rather obnoxious one. The bizarre outcome demonstrated for the first time that psychological processes such as personality have links to parts of the brain.

Studying damaged brains to understand normal brain function is an approach that strongly resonates with Julie Simpson, a molecular geneticist at UW–Madison. “We’re trying to do Phineas Gage for the fruit fly,” she says.

A postdoctoral researcher, Simpson works with laboratory tools that enable her to alter activity patterns in different brain regions of the common fruit fly Drosophila melanogaster. By monitoring what flies do when she genetically tweaks different brain parts, Simpson is trying to identify the precise genes, neurons and neural circuits that contribute to a range of fly behaviors. The work is painstaking, but already Simpson has identified neurons that may play a role in serious motor disorders such as epilepsy.

Piecing together the general principles that dictate the organization of a fly’s brain can dramatically aid in efforts to better understand human brains. “The fly is beautiful because it is simple and complicated at the same time,” says Simpson. “We have the tools to work on it, but at the same time it is complicated enough to serve as a good model for humans.”

Now, after four years in Madison, Simpson is gearing up for her biggest career move yet. The scientist will shift her research to Ashburn, Va. this summer to run a laboratory of her own at the $500 million Janelia Farm Research Campus, a new research facility launched by the Howard Hughes Medical Institute. “The opportunity is exactly tailored to my interests and I was incredibly lucky in terms of timing,” Simpson says. “This is really a chance of a lifetime.”

Followed by luck

In many ways, luck has complemented Simpson’s talent right from the start. Raised in Rockland County, N.Y., by parents who are scientists — her mother is a nurse and her father is a Columbia University geochemist — Simpson was quickly indoctrinated into the world of science. “Having a parent who’s a research scientist made me like that lifestyle a lot,” she says. “And both my parents feel strongly that we can’t be parasites on earth.”

An excellent biology teacher in high school also nurtured Simpson’s flair for science. “I’ve known since ninth grade that I wanted to study genetics. When we learned about Mendel’s experiment with peas, I thought it was the coolest thing since sliced bread,” she says. “I was one of the lucky ones who always knew what they wanted to do.”

As an undergraduate, Simpson studied molecular biology at Princeton University. It was there, while working in a neurogenetics laboratory, that Simpson first became acquainted with the vast biomedical promise of the fruit fly model. It was also the beginning of her quest to understand how neurons arrange themselves in organisms to give rise to distinct behaviors.

She went on to earn a doctorate from the University of California, Berkeley, before arriving at UW–Madison in 2001 to start a postdoctoral position under Barry Ganetzky, a geneticist.

“[Simpson] has chosen to embark on a very ambitious project but one that is of central importance to understanding the relationship between brains and behavior,” says Ganetzky, “I expect that Julie will become recognized as one of the leading investigators in this field.”

Focusing on the fruit fly locomotion system, Simpson has used several innovative genetic techniques to rear around 440 different fruit fly populations or “lines.” Each line carries a unique genetic mutation that Simpson has the ability to switch ‘on’ or ‘off’ at will. “What we’re asking is: What can’t the fly do if it’s not wired right? Does it suddenly get paralyzed or start to seize? Does it court like mad or start walking backwards?” Fruit flies carry around 13,000 genes, so Simpson has no illusions that she’ll be finding all the answers any time soon.

Working on the ‘fun stuff’

At Janelia Farm, which is to open in July, Simpson will serve as one of 24 multidisciplinary “group leaders” who will explore basic biomedical questions and imaging and computational technologies.

Simpson will have unlimited access to expensive instruments such as the confocal microscope, which is crucial for her work. She will also be free of the administrative, grant writing and teaching duties that mainstream academics constantly contend with. “I love that I won’t have to modify what I’m doing now,” she says. “I like dissecting fly brains! And I’m not ready to sit in my office and let other people do what I think is the fun stuff.”

As Simpson moves into the upper echelons of science, however, she is increasingly aware of the dearth of female scientists at the top. “I am very worried about the drop- off of women in higher-level science positions. I don’t understand it, I don’t know how to fix it, and I don’t like it,” she says. “I guess I am going to do what I’m going to do and hope that helps other women along the way.”