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SYSTEMS BIOLOGIST VAMSI MOOTHA | MEETING THE MINDS

He's at the forefront of a new science

On the otherwise austere walls of Dr. Vamsi Mootha's Massachusetts General Hospital office, there's a colorful painting of a French-Canadian lakeside village. It's a sunny, childlike composition, a patchwork of clear lines and primary colors. In the bottom left corner it shows a boy and a girl riding a bicycle, representing the artist's first two children, both of whom died of Leigh syndrome French-Canadian variant -- a rare genetic disease.

Mootha, an assistant professor at Harvard Medical School and at Mass. General, wrote a computer program to pinpoint the gene that causes the disease, leading to the development of a pre natal screening process for it. The bereaved mother underwent the screen and later delivered a healthy baby girl.

``It was amazingly satisfying to see the computational work I did have a real effect," says Mootha, who, at 35, maintains his penchant for racquet sports. Mootha was born outside Hyderabad in southern India. His family moved to the United States when he was 9 months old, and he grew up in the Texas oil town of Beaumont.

If there's a medical school gene, Mootha is a carrier. His father is a doctor, as are his two brothers, his sister, and all of their spouses. Naturally, ``when I was a kid, I wanted to be a doctor," he says.

High school, however, led him toward the more abstract beauties of pure mathematics, and he earned a computer science degree at Stanford University. ``It was really exciting to be in the computer field in Silicon Valley in 1993," he says with a smile. ``I was recruited by Wall Street. But then I took an introduction to biochemistry class."

He returned to the medical fold, but with his tastes sharpened for laboratory research. And it was as a first-year medical student at Harvard that he found his passion: mitochondria, the microscopic ``power plants" inside cells that convert food into energy.

He opens a book to a picture of a swarm of oval-shaped blobs. ``They're absolutely gorgeous," he says of images that might have been painted by the 19th-century Austrian master Gustav Klimt.

Mootha's lab studies mitochondria hoping to learn more about diseases such as diabetes and obesity. He approaches his research using systems biology, which looks at how collections of molecules work together, as opposed to simply delving into the nature of individual proteins. It's a new field -- one in which Mootha is a recognized leader -- and it demands a particular mental bent.

``It's a quantitative approach to biology," says Mootha, whose computer background has served him well in this cross-disciplinary field. ``We're living in an information-rich era. The mapping of the human genome is complete and we know what all the proteins are. Instead of asking how does one particular protein behave, we can ask how do all 22,000 proteins behave?" Harvard's systems biology department opened two years ago, and Mootha was one of the first on board. His work won him a $500,000 MacArthur ``genius" grant in 2004.

``It's important to have fun with your work," he says, and although complex systems biology may seem to be a peculiar definition of fun, Mootha certainly enjoys it. ``I'm a scientist, a manager, a fund-raiser, a teacher, and I see patients. It's a busy career, but I'm doing what makes me happy."

Looking up at the painting given to him by the mother of the children who died of Leigh syndrome, Mootha recalls the moment that the sequencing technician knocked on his door and handed him a piece of paper proving they had found the culprit gene. ``That was an exciting day, and this is a very exciting time to be in biology in Boston," he says. ``This is where it's all happening."

FACT SHEET

Hometown: Cambridge's Central Square. ``Between Central and Kendall Square and Charles/MGH, my life is on the Red Line."

Hobbies: Squash in the winter, tennis in the summer (he was on the JV team in college). Also, painting watercolors.

Ambitions: To improve diagnostics and therapeutics for diseases. And perhaps inspire a new generation of biologists.

Currently reading: Ben Mezrich's ``Bringing Down the House: The Inside Story of Six MIT Students Who Took Vegas for Millions." Also, ``The Plausibility of Life: Resolving Darwin's Dilemma" by Marc Kirschner and John Gerhart. (Kirschner is chairman of Mootha's Harvard department).

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