By William J. Cromie

Gazette Staff

Ernest Peralta eavesdrops on cells when they talk to themselves and to each other. He listens to heart cells, brain cells, and cells that secrete hormones that drive much of our behavior.

For what he's learned, the University recently appointed Peralta, 37, a professor of molecular and cellular biology.

When he came to Harvard in 1989 from Genentech, a San Francisco biotechnology company, Peralta thought of it as a good place to start. "Being on the faculty here makes it easy to get a job elsewhere," he said. "But after two years you realize how much you like it; after five years, it's very hard to leave. It's a great relief to get tenure, then you can concentrate all your energy on teaching and research."

"My colleagues and I in the Department of Molecular and

Cellular Biology are delighted that Ernie will be joining us as a permanent member of our faculty," commented Richard Losick, Maria Moors Cabot Professor of Biology. "Ernie does beautiful and insightful work. The Peralta laboratory is one of the most vibrant in the Department and a magnet for graduate students."

"Ernie is an extremely able and compatible young man," adds Guido Guidotti, Higgins Professor of Biochemistry. "Harvard is lucky to have recruited him, and even luckier that he stayed to get tenure. He puts the same enthusiasm into teaching large undergraduate and small specialty courses."

Jump Shots and Jumping Genes

Peralta grew up in Fort Wayne, Ind., where, he says, "you are judged by your jump shot." In high school, he played basketball and ran track. "Sports taught me discipline and how to budget my time," he remembers. "On the academic side, I found biology courses the most exciting."

Both his parents were immigrants. He describes his father as a "Filipino-Hispanic" and his mother as a "tall, green-eyed blonde from Latvia." "They were humble stock who valued education, and both earned their college degrees in this country. There was never any question that my three sisters and I would go to college."

Peralta enrolled at Northwestern University in Evanston, Ill., "The first week I was there, I took the bus home. I missed everyone and wanted a good home-cooked meal."

His interest in biology nudged Peralta toward medical school. "I worked part-time at Northwestern University's hospital and took the late shift to get more responsibility," he recalled. "But I found figuring out how the body works, or does not work, more exciting than practicing medicine. My parents supported my decision to go for a career in biology."

Peralta had interests other than science. He was only one course short of a second major in economics when he earned a B.A. in biochemistry in 1981.

"I chose Indiana University for graduate work because I was still a 'homeboy' at the time," Peralta notes. "And that school was strong in the things that interested me most -- immunology and jumping genes."

Jumping genes are sections of DNA that rearrange themselves, thereby changing the function of the gene of which they are part. Such changes are responsible for defending humans against an infinite range of viruses, bacteria, unfriendly protozoans, and other foreign invaders. Thanks to this mechanism, a relatively small group of general-purpose immune cells can transpose themselves into specialists capable of defending the body against a vast number of specific disease-causing organisms.

"When I first learned how this worked, I found it astonishing -- amazing." Peralta says. "I wrote my first paper on jumping genes."

Beyond the Midwest

During his second year of graduate school, Peralta's adviser failed in his bid for tenure. "I was shocked; I worshipped that man." Peralta recalled. "The incident made me rethink my decision to go for a career in academics. I took some time off and went to the south of France with my guitar. At the time, that was unthinkable at Indiana [University], but it reaffirmed my plans to continue working in cell biology."

After receiving a Ph.D. in 1986, Peralta decided to see the world beyond the Midwest. He took a job with Genentech on the West Coast. There, he focused on how cells talk to each other via chemical messages. Peralta concentrated on a messenger known as acetylcholine, which binds to receptor molecules on the surface of cells.

When Peralta started this work, biologists believed that acetylcholine attached itself to one kind of receptor and delivered one kind of message. But he discovered five receptors on a variety of cell types. On the surface, the receptors look the same, but they deliver different messages. In one case, brain cells record information. In another, heart cells slows the force and rapidity of a beat. In other situations, lung cells constrict, or endocrine cells release hormones.

"The company rewarded me," Peralta recalled. "I bought a VCR with the money. The first program I taped was that infamous game in 1986 when Billy Buckner committed the error that cost the Red Sox the World Series."

Peralta's work attracted enough attention for him to get offers of tenure at the age of 29. But he turned them down in favor of an assistant professorship at Harvard. "I was attracted by the quality of the faculty and students," he said.

His rise through the ranks was rapid, to associate professor in 1993, then full professor this year. "Of course, now I'm glad I made the choices I did, but there were times when I was not so sure."

For the past year and a half, Peralta has been eavesdropping on the cell talk that causes heart rates to slow down and speedup. Acetylcholine landing on a heart cell starts a complex chemical conversation that slows the strength and speed with which the heart pumps blood.

He masters the smallest details of such conversations by duplicating the genes responsible for making messages and the proteins that receive them. "We manipulate genes in ways that change the messages between cells," Peralta explains. "Then we put the 'foreign speaking' genes into cells and see what happens."

He and his students start with frog egg cells, because they are big and easy to work with. If things go well, the experiments move to rat and human cells.

Listening to heart cells gives Peralta general knowledge that he can also use to decipher conversations between messengers other than acetylcholine and receptors on brain and other cells. "It's a bonus," he says. "And the work has many medical applications including the possibility of developing better drugs for high blood pressure and migraine headaches."

Peralta communicates this knowledge to students via graduate and undergraduate courses. He coteaches Basic Principles of Biochemistry and Cell Biology with Higgins Professor of Biology Daniel Branton. He also teaches a graduate course on the molecular details of cell communication.

"I feel good about my teaching, and I received good ratings from students last year," he says. "But I'm not yet where I want to be. I'd like to be less of the Al Gore-type and more engaging with students. I think that will come with more experience."

Peralta believes that tenure will restore more balance to his life. "As junior faculty, you use all your time doing research, teaching, and writing grant proposals," he says. "Vacations have been limited to one week off during Christmas break."

He intends to spend more time with his wife, Renate, whom he met at Indiana University. A native of Germany, she freelances as a computer graphics artist. She did some of the illustrations for the latest edition of A Genetic Switch by Mark Ptashne, Herchel Smith Professor of Molecular Biology.

Peralta also sees more tennis games with his wife in the future, as well as more sharing of her love of art. And, of course, there will be more time to work on his jump shot.