Category Archives: Profiles

Cave detective hunts for clues to past sea level

A yellow splash of light from Bogdan Onac’s headlamp bounces around the dripping orange walls of a cave like a frenetic firefly. At the other end of the beam, the University of South Florida paleoclimatologist explains that the walls of this cave, on the Mediterranean island of Majorca, have collected a bathtub ring of minerals as brackish water washes in and out. “Majorca is like a Gruyère,” Onac says, its underlying limestone filled with holes just like the cheese.

Unlike most coastal cave sites around the world, Majorca sits on a stable tectonic plate and so can serve as a fixed point from which to measure the rise and fall of the sea over time. its caves became encrusted with marine minerals over the course of half a million years. High water marks remain, like graffiti from a changing climate.

A surprise in these cave walls has put Onac at the center of a debate about past sea levels. encrustations dating back 81,000 years at several of his research sites sit about a meter above present-day sea level, suggesting that’s how much higher the seas were then. This contradicts estimates of past sea levels…

See the rest of this profile, these photos, and more in Science News Prime: [html] [pdf]

Cameron Hummels in his observatory, 2009. Lucas Laursen for Science Careers.

Astronomer Finds Rewards in Outreach

Cameron Hummels in his observatory, 2009. Lucas Laursen for Science Careers.

The telescope room atop Pupin Hall at Columbia University offers a stunning view of the night sky and the New York City skyline. Astronomy Ph.D. candidate Cameron Hummels even considered moving his desk and computer up to the rooftop shed before concluding that his computer would not last long without heat or air conditioning. As much as Hummels would like to be near the telescopes all the time, the discoveries he wants to make also require computers, and there’s a lot at stake: “I love the fact that I could potentially make a difference,” he says, “in how we identify the underlying principles of nature.”

Read the whole story at ScienceCareers.org [html], a [pdf] or read the story behind the story here…

While Cameron was showing me around on the roof of the building, he found a $20 bill wedged in a hard-to-reach nook between a telescope dome and a brick wall. The incident didn’t make it directly into the story…but may have inspired the title.

Science Careers Kouzarides

Creativity and Persistence Overcome Failure

Science Careers KouzaridesTony Kouzarides tells the story of his early career as a comedy of errors. He started his Ph.D. at the University of Cambridge in the U.K. in 1981 studying the cancer-inducing potential of human cytomegalovirus. After a year of inserting part of the virus’s DNA into target cells, the cells showed almost no signs of cancer. He couldn’t rule out that other parts of the virus might do it, but he also couldn’t publish his early results. What he could publish by the end had more to do with genetic sequencing, an area he did not want to pursue.

After a short postdoc at Cambridge sequencing cytomegalovirus, he landed a second postdoc in a lab in New York studying oncogenes. There, he spent 2 years developing an unconfirmed and unpublishable hunch. On the strength of that record, he deadpans, he unsuccessfully applied to lead his own research group.

Finally, during the third year of his postdoc, Kouzarides read an article that sparked the connection he needed to do experiments that produced two top-tier publications. Soon after, he secured his current position as a group leader at the Gurdon Institute at Cambridge.

He calls it serendipity. Kouzarides’s lifelong friend and colleague Keith Blundy says Kouzarides’s secret is that “he’s a fantastic people person.” But there’s more to Kouzarides than charisma and good luck. Kouzarides also has a strong commitment to asking what he calls the “right questions” and an unusual willingness to bet on his instincts.

A fragile start

The fear of a null result is sickeningly familiar to most science graduate students. But, Kouzarides says, “partly, it’s almost irrelevant how well you do in your Ph.D.,” because “once you do your postdoc you really have to prove yourself again.”

He didn’t know that yet when he was still a student, so he faced a tough decision when his first project nose-dived. His supervisor, Tony Minson in the Department of Pathology at Cambridge, says that during Kouzarides’s second year, “it became apparent to him and to me that this virus was hundreds of times slower” than they had expected. Kouzarides saved his research project by arranging to work with Bart Barrell’s sequencing group in Cambridge’s Laboratory of Molecular Biology, where he sequenced parts of the virus’s DNA. That decision was “very unusual for a student” to make on his own initiative, Minson says, but Kouzarides was “clear-thinking and independent” from the beginning. “I take no credit!” says Minson.

Kouzarides’s clear-minded impulse led to some good interdisciplinary science, says Barrell, now at the Sanger Institute. “It was good for Tony to come over,” says Barrell, whose group consisted of sequencing specialists, “because he brought the biology over. We probably got a lot more publications out of cytomegalovirus because of him.”

Betting on himself

To capitalize on the virus-sequencing project he’d begun halfway through his Ph.D., Kouzarides did a short postdoc with Barrell. And although Kouzarides was relieved that his sequencing work was paying off in terms of publications, it wasn’t what he wanted to do in the long run. “I really was much more interested in oncogenes,” he says. So he arranged to do a postdoc with Edward Ziff, now a biochemistry professor at New York University’s Langone Medical Center.

Ziff had been working on the c-fos gene, which other researchers had shown was oncogenic, “but nobody knew how it worked or caused oncogenesis,” Kouzarides says. “My job was to find out why.” He identified a short stretch of its sequence that repeatedly coded for leucine, an amino acid. He hypothesized that these leucine repeats permitted the protein to interact with itself or other proteins necessary for cancerous replication. But there was a problem: He had no evidence that it did either.

After his second year in New York, Kouzarides says he was thinking, “Well, I’ve got no results, but I have a lot of publications from my first postdoc and Ph.D.,” so he began applying for jobs. He was able to get a tenure-track job offer, but it was “not in the field that I was interested in. My career would have been about viruses, but I was interested in cancer.” He bravely passed on the offer and went back to New York for a third year to pursue his c-fos project. “I was really passionate, and I really believed in this hypothesis based on no data!” he marvels now.

The decision paid off that year when he read a paper that showed that c-jun, another gene, had similar leucine repeats. He was able to show that the leucine repeats on c-jun and c-fos “zipped” the proteins together—evidence that C-FOS proteins could interact with other proteins involved in cancerous cell replication. Two Nature papers later, he was able to secure a group leader position back at Cambridge, where he’s been ever since.

Asking the right questions

In 1998, Kouzarides approached the technology arm of his major funding source, the charity Cancer Research UK, about developing medical treatments from his work. His case was assigned to his friend Blundy, then a technology transfer manager at Cancer Research Technology, who was charged with helping him create a commercial spinoff. Nobody was more surprised than Blundy by Kouzarides’s entrepreneurialism. “I don’t remember him being a commercial animal at all,” Blundy says. But Kouzarides’s networking skills and his willingness to let other experts handle the commercial side made the launch a smooth one. The result was Chroma Therapeutics, a drug-discovery and development company with nearly a dozen products in the pipeline today.

Now that Kouzarides’s career is reasonably secure, he can afford to devote more effort to his supervisees. An important part of his job, he says, is to help new postdocs “refocus, to make sure that the path they take is the path in the right direction rather than veering off toward some nonproductive area.” One wall in Kouzarides’s office testifies to his success as a supervisor. It contains neatly mounted photos of grad students and postdocs celebrating holidays, lab retreats, and the first two quintennial lab reunions he’s hosted. At the reunions, dozens of new principal investigators and other former members of his lab converge around him to discuss their work and catch up with one another. Kouzarides cultivates “fantastic camaraderie” in the lab, Blundy says. Kouzarides says, “We have a lot of fun together; … it is like a big family.”

Kouzarides’s main piece of advice to his younger colleagues in the lab is to stop and think about the questions they are asking. “Spend as much time as you like thinking about the experiment because if you waste your time doing the wrong experiment, you might as well not do it at all,” he says. “Only do the key experiments for the very important questions!” The details are best left to others. He sets the example by taking the members of his lab on an annual retreat to reflect on the state of their work and make plans for the coming year. Kouzarides remains as willing as ever to turn on a dime to pursue a new idea. “His lab is willing to drop everything and take a new direction” when a good opportunity comes up, Blundy says.

Kouzarides says it’s hard to overestimate the importance of originality and independent thinking: “Formulate your own questions that haven’t been addressed yet.”

First published by Science Careers [html] [pdf]

Addendum: I first encountered Kouzarides at a symposium for Ph.D. students in Cambridge. He was behind a lectern, grinning mischievously and showing photos of one of himself and a university mate to the students while he recounted the tortured story of his ascent to scientific stardom. At the same time, he’s the first to admit that he’s had it good: he’s now a group leader at the Gurdon Institute here in Cambridge, where he’s been nearly all is his professional career. What struck me about him at the symposium was his ability to spin the yarn of  his early career failures cheerfully, and the admission that failure really is a natural part of the scientific process. Like any former wannabe scientist, I relish stories of failure.

Thomas Helleday in his laboratory, 2009. Lucas Laursen for Science Careers.

Young Swedish Scientist Reveals Fast-Track Career Secrets

Thomas Helleday in his laboratory, 2009. Lucas Laursen for Science Careers.

Thomas Helleday was precocious long before he started supervising Ph.D. students as he finished his own doctorate. His mother, a banker, bought him his first stock at age 7. At age 16, the Swedish native volunteered in a cancer ward with his older brother and “was terrified” by the harsh side effects of radiation therapy he saw there. Vowing to do something about it, potentially in the pharmaceutical industry, Helleday studied business and molecular biology as an undergraduate.

By the time he turned 35, Helleday was a full professor and laboratory head at two institutions in two countries. He had hunted Soviet subs in the Baltic Sea, lost a small fortune in the 2000 stock market crash, racked up a series of awards for young investigators, and authored numerous papers in top journals.

Helleday shrugs off his achievements, smiling. He is too busy moving his Oxford research group into new facilities to spend much time looking back. He arrived at the University of Oxford just over a year ago, and his new lab, surreally pristine, will house his seven-strong research team. He returns to Sweden monthly to supervise his other research group of 15 at Stockholm University. Between commuting, conferences, and lectures, Helleday says, he is on an airplane almost every week.

He has demanded much from himself and his colleagues ever since he was young. “I wanted to make a difference,” he says, but it’s possible he didn’t anticipate how much his success would demand of him. “If I don’t do my job, the people working for me will not have papers and their careers will be spoiled. So everybody’s pushing the leader, … so I have to work harder.”

Student of biology

By the time Helleday finished his twin undergraduate degrees at Stockholm University, he was reconsidering his plans for a career in the pharmaceutical industry. “They wanted me to sell pills, told me everyone started like that,” he says. At that point, he “realized I needed a Ph.D. to pursue my own ideas.” One of his professors, Dag Jenssen, persuaded Helleday to join his lab in the Department of Genetics, Microbiology, and Toxicology at Stockholm University to investigate the importance of recombination in somatic cells, tumor cells, and cancer initiation.

When Helleday began his graduate studies, Jenssen was working half-time at the university, devoting the rest of his time to a commercial venture. Helleday stepped in and supervised other Ph.D. students in the lab, and he also obtained funding for his own independent project. Helleday wears his can-do attitude on his sleeve, which some of his peers found frustrating. “He was almost too enthusiastic,” Jenssen says, “and people thought that was a little hard to take.” But others embraced Helleday’s knowledge and willingness to share. “He is like a book,” Jenssen says. “Other people asked for supervision from him because he knows a lot.” Jenssen did his part to strengthen Helleday’s managing style by “inform[ing] him about the unwritten laws within academic life.”

So, Helleday was already comfortable as a supervisor by the time he landed in Mark Meuth’s lab at the University of Sheffield in 1999 as a postdoc. There, Helleday began investigating inhibitors of an enzyme called PARP, which contributes to DNA repair. Inhibiting this enzyme in certain defective cancer cells prevents them from replicating. Meuth calls PARP-inhibitor research a “graveyard of investigators,” but Meuth indulged his ambitious postdoc.

Within a year, though, Helleday says he wanted do his “own thing” with PARP, so he obtained start-up funding from the medical research charity Yorkshire Cancer Research and applied for an opening at Sheffield to start his own lab while continuing to supervise the Stockholm lab he founded as a graduate student. Meuth says that Helleday’s success at Sheffield was partly luck but that he was definitely qualified for the job.

Helleday’s groups focus on finding novel treatments that target the DNA damage usually found in tumor cells but not in healthy cells. One of Helleday’s projects focuses on cancers caused by a rare defect in a tumor-suppressor gene; women with defective versions of the gene have up to an 80% increased risk of breast or ovarian cancer. “It’s a tragedy for these families,” says Helleday. “Some of the women die very young.” In lab experiments, his group found that PARP inhibitors killed tumors with the defect. The results were published in Nature in 2005 with Helleday as senior author, and PARP inhibitors are now being tested in clinical trials. The PARP-inhibiting drug “doesn’t have many side effects because it’s a protein that’s normally not required by the rest of the body,” Helleday says. So in that case at least, Helleday achieved his childhood goal of alleviating the side effects of cancer treatment.

Helleday is motivated by the practical benefits of his research, but he also points to the pleasure of cracking biological mysteries. “You come up with a really simple model … and then you see that it all fits and it’s all so beautiful and you just know that it’s correct.”

Student of life

Helleday’s early willingness to learn lessons firsthand has contributed to his scientific success. He calls those first years running his own labs “the most eye-opening time of my career.” He says he’s glad he took on responsibility early in his career and worries that some students and postdocs “are kind of spoon-fed, and I think that is not a good thing if you want to develop an independent career.”

The laboratory didn’t provide Helleday with his first lessons in leadership. He was fresh out of high school when he volunteered as a sonar operator in the Swedish navy for his national service at the tail end of the Cold War. He was disappointed when his “alcoholic” shipmates couldn’t keep the sonar from listing long enough for him to get an accurate sonar ping. “How the hell was I going to find a sub?” he growls, recalling the incident.

“I was irritated by these kinds of things and I shouldn’t have been. I was questioning … how the boat was run.” The old hands didn’t appreciate his interference and treated him like an outsider. Helleday still puts a lot of enthusiasm into his work, but those past experiences taught him not to overwhelm his junior colleagues. “What I do is that if they have developed an area and become very good at it, then I step aside. I have so much cooking,” says Helleday, “that I can leave that pot to someone else.”

One area that is a bit of a challenge for Helleday is his work-life balance: His wife, Clara, says neither of them has had time for hobbies since the birth of their 17-month-old daughter. “I’ve always said to my wife that I should probably not work too hard and have a little more time with family, but it’s always gone in the other direction,” muses Helleday. He used to sail and go salsa dancing with his wife, but he only gets out on the water about once a year now, and he’s not completely happy about it. “I want to be dancing,” he chuckles. “I want to enjoy life!”

With two tenured academic appointments, many widely cited papers, and five European young researcher awards, Helleday could probably sit back and enjoy life a little more. But he points out that those awards didn’t walk in the door. “I think that a lot of people are sitting there waiting to be discovered,” he says, but that waiting isn’t enough. “You have to promote yourself, and that’s hard.” Helleday’s diligence has been a big part of his success, but he also advises new managers not to try to be an overcommitted “superpostdoc” by trying too hard to do lab science and science management. He says, “A young manager needs to get away from the lab and free up time to think instead of working in the lab themselves.”

First published in Science Careers [html] [pdf]

My first science-related writing assignment that included travel and an in-person interview. I took the bus to Oxford, made the long slog on foot to Helleday’s lab, and interviewed him and a postdoc he works with. I’m afraid the story doesn’t really convey how much energy the guy has. He’s one of these dynamo types who probably has room in his life for several careers. After sampling a few pretty unrelated things including painting watercolors and the naval branch of the Swedish intelligence service, Helleday settled down to the thing he’s always wanted to do: fight cancer. Of course, one lab wasn’t enough, so he runs two in parallel. Maybe someday I should visit his Stockholm lab for another story.