October 12, 2009

Our newest Nobelist: Carol Greider

Carol Greider honored for her groundbreaking work on telomeres

Carol W. Greider, Nobel Prize winnerCarol Greider, a self-described early riser, was folding her laundry and preparing to go to a morning spinning class when she learned that she had just been named co-winner of a Nobel Prize—and had 45 minutes to get ready for the official announcement. Talk about a change in plans.

“My heart just really started racing at that time,” said Greider, the Daniel Nathans Professor and director of Molecular Biology and Genetics in the Johns Hopkins Institute for Basic Biomedical Sciences.

Greider, 48, one of the world’s pioneering researchers on the structure of chromosome ends known as telomeres, was awarded the 2009 Nobel Prize in physiology or medicine by the Royal Swedish Academy of Sciences on Monday, Oct. 5.

The academy recognized her for the 1984 discovery of telomerase, an enzyme that maintains the length and integrity of chromosome ends and is critical for the health and survival of all living cells and organisms.

She became the 33rd person associated with Johns Hopkins University to win a Nobel Prize and the 20th at the School of Medicine to receive the honor.

Her excitement clearly had not worn off hours later at a press conference, held at the School of Medicine’s Tilghman Auditorium.

Greider thanked the Nobel committee and praised her “telomerase colleagues” at Johns Hopkins and around the world for making the award possible.

“I think what has happened today is really a tribute to curiosity-driven basic science,” said Greider, who was joined at the event by her two children, Charles, 13, and Gwendolyn, 9. Also in attendance were Ronald J. Daniels, university president; Chi Dang, vice dean for research at the School of Medicine; and Peter Agre, director of the Johns Hopkins Malaria Research Institute and 2003 recipient of the Nobel Prize in chemistry for his discovery of aquaporins.

Daniels told those gathered how thrilled he was at the announcement.

“It will come as no surprise that there can be no greater pleasure than joining the Nobel committee in honoring the work of one of our outstanding faculty members,” Daniels said. “Carol, on behalf of all your colleagues, we bask in your glow. We are so proud of you, and we are so thrilled that this well-deserved honor has come your way.”

Daniels then joked that Greider’s children had better prepare for life with a Nobel Prize–winning mom.

“I told both of them already, Guys, you have to treat a Nobel laureate with a much greater degree of respect,” he said. “There will be extra dishwashing duty.”

Greider shares this year’s prize with Elizabeth Blackburn, a professor of biochemistry and biophysics at the University of California, San Francisco, and Jack Szostak, of Harvard Medical School, who discovered that telomeres are made up of simple, repeating blocks of DNA and that they are found in all organisms. Greider, Blackburn and Szostak shared the 2006 Albert Lasker Award for Basic Medical Research for this work.

At the press conference, Peter Agre took a moment to congratulate his fellow Nobelist.

“First off, the Nobel committee always says how their deliberations are really difficult. Well, this year it was really easy, Carol,” Agre said.

Considered the most prestigious honor in the world, the Nobel Prize has been awarded for achievements in physics, chemistry, physiology or medicine, literature and peace since 1901 by the Nobel Foundation in Stockholm, Sweden. Greider, Blackburn and Szostak each will receive a medal and diploma and will share a cash award of 10 million krona ($1.4 million) at a ceremony on Dec. 10 in Stockholm.

“This is a wonderful moment,” Daniels wrote in an early-morning e-mail announcement to the university community, “not only for Dr. Greider but also for all of us here at Johns Hopkins who share in her passion for discovery and her zeal for putting knowledge to work for the good of humanity. We are thrilled by this magnificent accomplishment of Carol and her colleagues and even more so by the implications of her continuing work for our understanding of such complex problems as cancer and aging. Carol has advanced scientific knowledge immeasurably, but she remains unsatisfied and wants to know more. That is the Johns Hopkins way.”

Each time a cell divides, its chromosomes become a little shorter. As cells age, their telomeres shorten. The consequent loss of telomere function will cause some cells to stop dividing or to die, and others to undergo chromosome rearrangements that can lead to cancer.

Greider, Blackburn and Szostak performed their groundbreaking investigations in the late 1970s and the 1980s. Blackburn showed that simple, repeated DNA sequences make up chromosome ends and, with Szostak, established that these repeated sequences stabilize chromosomes and prevent them from becoming damaged. Szostak and Blackburn predicted the existence of an enzyme that would add the sequences to chromosome termini.

While a 23-year-old graduate student with Blackburn, who was then a member of the faculty at the University of California, Berkeley, Greider tracked down the enzyme telomerase, and later determined that each organism’s telomerase contains an RNA component that serves as a template for the creature’s particular telomere DNA repeat sequence. In addition to providing insight into how chromosome ends are maintained, Blackburn, Greider and Szostak’s work laid the foundation for studies that have linked telomerase and telomeres to human cancer and age-related conditions.

A delighted Greider thanked the Nobel Foundation for the award and emphasized that the recognition highlights the value of “discoveries driven by pure curiosity.”

“We didn’t know at the time that there were any particular disease implications [in our research]. We were just interested in the fundamental questions of cell biology,” she said.

“Really, it was just trying to understand how cells work,” she said. “From a disease aspect, I liken it to a car mechanic and a broken-down car. If you never knew how the carburetor worked, you would not be able to figure out why that car isn’t working. We are there to figure out the basics of how cells actually work so that in disease you can figure out what went wrong.”

Greider worked with a single-celled, pond-dwelling organism called Tetrahymena. These organisms—rather than primates or humans—were the best test system, she said, because Tetrahymena contain “more like 40,000 chromosomes, compared to our 23 pairs” and thus have far more chromosome ends to study.

Stephen Desiderio, director of the Institute for Basic Biomedical Sciences at Johns Hopkins, said, “The most far-reaching discoveries are the product of basic research. We are thrilled that Carol is being recognized for her work, which reminds us that science is most powerful when it is driven by curiosity.”

Greider grew up in Davis, Calif., where her father was a physicist at the University of California. Greider credits her parents for her decision to go into science, and her father for influencing her attitude about academic science.

“My father would talk about academic freedom and the importance of liking what you do. He would say, ‘You can do whatever you want, but you have to like whatever you do.’ ”

She graduated from the University of California, Santa Barbara, with a bachelor’s degree in biology in 1983 and earned her doctorate in molecular biology in 1987 from Berkeley. She worked at Cold Spring Harbor Laboratory on Long Island, N.Y., from 1988 to 1997, first as a postdoctoral fellow, then as an associate investigator. She moved to Johns Hopkins in 1997.

While at Cold Spring Harbor, Greider, working with Calvin Harley of McMaster University, realized that cancer cells, unlike most cells in the adult human body, contain active forms of telomerase that enable cells to keep dividing by maintaining the length of their chromosome ends. Together, in 1990, the two scientists provided early evidence that telomere length was related to cellular aging. They found that telomerase is activated in cancer cells, a process that allows these cells to bypass cellular senescence and continue growing as immortalized cells.

The two researchers began to imagine a treatment for cancer in which the telomerase could be inhibited long enough to wipe out the telomeres in the malignant cells. This would trigger death in the cancer cells but not in normal ones, with their longer telomeres.

Subsequent work using cultured human cells and mice genetically engineered to lack the gene for telomerase confirmed that inhibition of telomerase can limit cancer cell division and tumor production.

Greider continues to study the role of telomeres in DNA damage and cell death. Recently, she and her colleagues developed a mouse model for a rare, inherited disorder related to stem cell failure, dyskeratosis congenita, that is caused by mutations in telomerase. People with dyskeratosis congenita cannot maintain the telomerase in their bone marrow and eventually die of bone marrow failure.

“Suddenly, the studies that we had done on the consequences of telomerase loss were pertinent to this disease,” Greider said. “It’s another example of curiosity-driven research ending up having a direct medical implication.”

Greider is currently working on mouse models she helped develop to understand how telomerase may play a role in both cancer and stem cell failure. This might lead to a clearer link between aging and telomeres, she says. “I don’t believe that aging is going to be a matter of just one thing, that there’s going to be one gene that controls all of aging. I think there are going to be multiple different failures, and that the loss of stem cells can play a role in a number of them.”

For more about Greider and her work, go to http://webapps.jhu.edu/jhuniverse/featured/ 2009NobelMedicine.