Striving to answer life's basic questions

Hopkins researcher looks to a worm's reproduction to unlock scientific secrets

Profile / Geraldine Seydoux


Geraldine Seydoux studies what happens when a new life begins to unfold.

Seydoux is a geneticist at the Johns Hopkins School of Medicine, a recipient of a MacArthur "genius" award and an investigator at the prestigious Howard Hughes Medical Institute. She is also an enthusiastic researcher who has spent nearly 20 years studying a microscopic worm, Caenorhabditis elegans, and has yet to tire of it.

She and others like her are convinced that it has secrets to share about life's basic questions.

"It's like this animal is screaming a message at you, and sometimes you have to pay close attention to hear it," she said.

The worms make ideal lab rats and are used to study cancer, aging and evolution, among other topics. They are transparent, reproduce quickly, have a nervous system and can be stored easily in refrigerator-sized incubators. They also share many of our genes, tracing their ancestry to the same one-celled organisms that dominated the planet millions of years ago.

Seydoux's work focuses on C. elegans' reproductive system.

It's basic biology that sperm and egg combine to make an embryo - which in turn develops into all of the cells in our bodies.

The process is the same for humans, worms and almost everything else. The worm's conception process is, in some ways, similar to what happens inside any mother - the worm creates an embryo out of a fundamental type of cell called an oocyte, which transforms into an egg.

Seydoux has spent years focused on the cell's transition from oocyte to embryo. The oocyte, she says, is something special.

"This is the only cell in our body that does this, reprograms itself so that it can become something else," she said.

Her work has implications for cloning research. Researchers who have so far duplicated sheep, dogs, horses and cats have done so by working with oocytes.

But Seydoux is not as interested in cloning as in addressing issues of conception. How does the sperm interact with the egg to make an embryo? How does the egg prepare for it?

Seydoux discovered this year that, at least in the worm, the oocyte begins its transformation into an egg in the moments before fertilization, with proteins gearing up to start embryo development, independent of the sperm. A paper detailing her work, published in Current Biology, was not a major breakthrough, but added a sliver of knowledge to what scientists know about C. elegans.

And that's how science progresses. Research can takes months or years. Results are often incremental.

"It can be at least a year, more often two or three years. But you get little nuggets along the way. It's enough to keep you excited enough about coming back to work every day," she said.

Seydoux came to Johns Hopkins School of Medicine in 1995 after earning a doctorate in genetics at Princeton University and doing postdoctoral research at the Carnegie Institution, a privately funded research facility with a branch on the Homewood campus of the Johns Hopkins University.

She teaches molecular science and genetics to medical students and doctoral candidates and oversees eight graduate students and researchers in her lab. The constant, probing questions from a new crop of students each year keep her sharp, she says.

"It's rewarding to have students who are really interested in what you teach and who want to know more," she said. "Sometimes, they'll ask a question you don't know the answer to and you have to take time and look it up."

Seydoux, 41, thought briefly about being a lawyer in her youth. But she began leaning toward a career as a scientist when a biochemistry professor at the University of Maine steered her toward summer internships in science labs. She spent one summer studying muscle biology at the Medical University of South Carolina and the next analyzing the genes that yeast use to mate at Cold Spring Harbor on Long Island.

Once at Princeton, she survived five years the way most graduate students in the sciences do now - on a stipend of about $12,000 a year paid by the university. (The stipend for doctoral candidates at the medical school is currently $25,200). It's a career path she highly recommends.

Seydoux, who serves on the admissions committee for doctoral candidates at the medical school, was pretty much a straight-A student all through school, getting only two Bs in four years at the University of Maine. But being a good researcher is less a matter of brains than intellectual curiosity, she says.

"It's about being passionate and persistent. What we want is the student who's excited about the question, who wants to find the answer and is the one who will be in the lab on Friday night to get the answer," she said.

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