Been there, done that. Biochemist-in-training Bridget Williams tells other students the good, the bad, and the ugly about getting a Ph.D. in science.

Her labmates nicknamed her Sensei, which means "mentor" in Japanese. Bridget Williams (pictured left), a 28-year-old biochemistry graduate student at Tulane University Health Sciences Center in New Orleans, Louisiana, is often the first person peers seek out for advice on their science--or life in general. She's also a favorite source of encouragement among minority research interns who visit Tulane in a summer undergraduate program called SPRITE.

Her role as a counselor to fellow scientists might come as a surprise at first because Williams, a tall African American with a beaming smile and a melodious laugh, has a shy and unassuming disposition. "If you walked into a [crowded] room, she would not necessarily be one of the first persons you met," says molecular biologist Valerie Wilson, director of SPRITE, which stands for Summer Pipeline Research Initiative: The Tulane Experience.

But Williams carries a calmness and confidence that draws people to her, says Wilson. "[If] you got to meet her and know her, [you] would just be immediately taken by her sincerity and the fact that she's very serious about what she's been doing. ... She's got a very positive approach to meeting challenges both in research and in other aspects of graduate life. So you get the sense that there's a solid rock in there."

Although Williams has always worked hard and earned excellent grades, her steadfastness comes from a graduate training experience that has seen its share of ups and downs. She is in her seventh year as a Ph.D. candidate in the laboratory of molecular geneticist Arthur Lustig, whose group studies mechanisms that control the size of telomeres, the protein-and-DNA caps that protect chromosome tips. But the finish line is finally within sight: Williams expects to complete her doctorate later this year.

By the time she is officially ordained as a scientist--the first in her family--she'll have traveled a long way from her childhood home in northwest Louisiana. She grew up in Shongaloo, a rural town of about 400 residents, where her father was a road construction worker and her mother held a job with a glove factory. Williams got hooked on science in fourth grade, when she and her fellow students did the classic experiment of soaking a chicken bone in vinegar for a few days, turning it soft and flexible. "I remember thinking then and there, 'Wow, I want to go into science one day,' even though I didn't really understand what that meant," she recalls.

Williams went on to attend Xavier University, a Catholic, historically black college in New Orleans. In her first year, she learned of Xavier's Minority Access to Research Careers (MARC) program, which is funded by the National Institute of General Medical Sciences (NIGMS), a branch of the National Institutes of Health (NIH). MARC encourages underrepresented minorities to pursue scientific careers by providing financial support and arranging research opportunities. "I joined the program, and the rest is history," Williams says. She worked in a chemistry lab at Xavier during the school year and spent her summers doing research internships at the University of Cincinnati in Ohio, Purdue University in West Lafayette, Indiana, and NIH in Bethesda, Maryland.

After graduating in 1996, Williams headed a few miles down the road to Tulane, joining Lustig's lab the following year. Many researchers were interested in understanding how an enzyme called telomerase replenishes telomeres, which would otherwise shorten with each cell division, eventually triggering senescence (see "More Than a Sum of Our Cells"). But Lustig was investigating how the cell keeps chromosome ends from growing to excess under telomerase's influence. By creating beefed-up telomeres and putting them into normal yeast, his group had just discovered telomeric rapid deletion (TRD), a process that trims overlong telomeres. Williams tackled her dissertation project with enthusiasm, attempting to identify mutations that cause defective TRD in yeast. Yet by 1998, her experiments weren't producing results, and Williams began to have serious second thoughts about becoming a scientist. "I just got really down and out about it," she says. "It led me to question whether or not this was for me."

But after Williams switched to a different project--investigating the internal stability of telomeric repeat sequences--things began to look up. "I got my confidence back, and that's when I decided that I wanted to stay in for the long haul," she says. That line of inquiry stalled too, however, because the data were difficult to interpret, so at the end of 2001, Williams again redirected her focus toward a protein called Mre11, which is required for TRD. In work funded by a National Research Service Award from NIGMS, she has been conducting mutational analyses of the protein to elucidate its role in telomere size control.

"She's been through a couple of bumps, and I think it's made her stronger," says Wilson. "I often tell people that you only learn half of what you need to know when you're always successful. You learn the other part of what you need to know when you're not--because then you'll learn how to overcome that and move on to the next level. I think that more or less describes that sense of certainty, that sense of determination that Bridget's got."

Her research on Mre11 is "going very well right now, and she'll have made a highly important contribution" by the time she completes her Ph.D., Lustig says. Williams is not only very self-motivated and willing to put in long hours, but in recent years she also has developed a knack for designing innovative research schemes. Occasionally, Lustig says, when she proposes an experiment, he initially views the idea with skepticism. "But then I think it through more and she's right. ... That's the point that you want students to grow to: where they can challenge your ideas."

Williams agrees that she has matured in many ways as a scientist. "I've learned how to deal with frustration and that you can't give up," she says. "If you really want to do something, you can get it achieved. ... I also learned that ... you can't let that one experiment keep you depressed for days and days; you've got to learn how to work your way out of it."

She is eager to share her experiences and knowledge with others. When she was an undergraduate at Xavier, people from her church asked her to tutor their children in math or science, which she did: "Any time I see I can maybe help someone, I'll just try to give a hand." Working with her husband, Chris Simmons, a Web entrepreneur and a research technician in an infectious-disease lab, Williams also hopes to develop a Web site to inform the African-American community about diseases that disproportionately affect them, such as diabetes and HIV infection.

Helping bring more people of color into research is important to her too. Growing up, she didn't know much about scientific career opportunities because there were no scientists in her life, says Williams. African-American children, teens, and college students might be more likely to choose a research career if they see investigators who look like they do, she adds.

In 1999, Williams was one of the first grad students to volunteer with SPRITE, which brings a half-dozen Xavier undergraduates to Tulane for 10 weeks of biomedical research. "She is wonderful; she is the star mentor to our students," says Charles Allen III, SPRITE program coordinator. Williams stays in close touch with the people she's shepherding, giving them pep talks when they run into issues in the lab.

One SPRITE student, Allen recalls, had been waitlisted by Tulane's molecular biology Ph.D. program, and as the summer wore on without any word about her application, she grew anxious about her future. "In her own mind, she was about to give up," he says, but Williams reassured her that as long as she had the drive and desire to pursue a science career, it would happen. "Bridget soothed her, calmed her down, tried to help her focus," says Allen. Just before the program ended, Tulane notified the Xavier student that she had been accepted.

Williams says she always tells people, "If I can do it, you can do it." Looking back at her own frustrations at the bench, she has no regrets about sticking with her Ph.D. program. "Yes, it's been hard, but I'm so glad that I stayed ... because I don't like to give up on things." She doesn't know exactly where she'll find herself 5 or 10 years from now, but she plans to pursue research and, not surprisingly, she also has aspirations of teaching. Says Williams, "I can see myself ... working with students, making sure they know what kinds of opportunities are out there, and trying to encourage them to shoot for the stars."

* Ingfei Chen, a contributing editor for SAGE KE in Santa Cruz, California, could use a sensei too.