Nobel laureate Venki Ramakrishnan sits at a dining table in the airy, top-floor canteen of the Medical Research Council (MRC) Laboratory of Molecular Biology (LMB) in Cambridge, U.K. A buzz of lively conversation rises from the table. It's morning tea break, and the room is full of researchers. To a British observer, there's nothing unusual about this scene. "Every university department has tea breaks. All of England has tea breaks," Ramakrishnan says.

This typical, casual canteen chat only partly reveals the facility's successful lab culture, which encouraged Ramakrishnan to focus on understanding the ribosome, the cellular machinery that turns RNA into protein. The work won Ramakrishnan a share of the Nobel Prize in chemistry 2009.

He's hardly alone. MRC LMB is among the world's most successful research centers as judged by its number of Nobel laureates. LMB lists (see box) 13 in-house scientists sharing nine Nobel Prizes since the laboratory was founded by MRC in 1947, among them Francis Crick and James Watson, who received the prize in 1962 for unraveling the structure of DNA.

This isn't a world record for Nobel wins. But where other centers may hire established scientists who have already done Nobel-quality work, "generally, the Nobel Prizes we've won have been for work done here," LMB Director Hugh Pelham says.

Bright young things

One way to run a successful research center is buying in what Pelham terms "empire builders" -- established scientists already running large research groups elsewhere. But most of LMB's recruits are promising young researchers. "Ideally, we'd like to hire people in their early 30s or occasionally even younger," Pelham says. Some new heads of research teams have come straight from earning a Ph.D.

One young recruit was Jason Chin, who was invited to start a research group after giving a talk at LMB when he was just a few months into a postdoc at The Scripps Research Institute in San Diego, California. Chin finished his postdoc, joined LMB in 2003, then last year won the European Molecular Biology Organization gold medal for his work in synthetic biology. (Read more about him in this previous Science Careers article.)


Jason Chin (CREDIT: MRC Laboratory of Molecular Biology)

Chin is just one example of the lab's successful, and early, talent spotting. The lab often identifies promising young scientists through personal recommendations or first-hand observation, at conferences, for example. "We listen to them at talks, have them visit to talk about their goals and ideas, and get a feel for whether they're good," Ramakrishnan says. "Talking to them is very important. Smart people stand out," Pelham says, then adds that they don't get it right every time.

To be of interest to LMB, young scientists should have done important or original work in more than one scientific setting. But important research doesn't necessarily mean a paper in Cell. "We don't really care if they've had a high-profile paper," Ramakrishnan says. "We go less by publications and are more willing to use our own criteria, of which an important component is that they should be interested in a long-term, challenging goal."

The laboratory uses a U.S.-style tenure system -- MRC's Programme Leader-Track (PLT) scheme -- to train new early-career group leaders and weed out unproductive people. About a fifth of the leaders of 'LMB's more than 50 research groups are currently PLTs, with 80% of the rest having already passed through the program.

All PLTs have a midterm review, where they give a presentation and are quizzed by Pelham and the heads of LMB's four divisions: cell biology, neurobiology, protein and nucleic acid chemistry, and structural studies. Like all LMB staff members, they have an annual appraisal. "By these means, we let PLTs know what we expect and what we value," Pelham says. Unlike many tenure calendars, the PLT schedule is flexible; at any point during the first 6 years, the laboratory can award a permanent position. Most succeed, but some have to leave, Pelham adds.


Hugh Pelham (CREDIT: MRC Laboratory of Molecular Biology)

Tea-break triumphs

Also important is inspiring and guiding younger researchers to do great work. One way this is done is through LMB's collaborative, informal culture. The tea breaks are a good example. "There are senior investigators sitting with first-year graduate students," Ramakrishnan says.

Asking anyone for help is encouraged. Pelham says that, as a recently tenured group leader, he learned yeast genetics through discussions with people in another research group. For students, it's "totally acceptable" to ask a senior researcher who isn't your own supervisor about your problem, says Rebecca Voorhees, who has just finished a Ph.D. and is now a postdoc in Ramakrishnan's research group. "That's the collaborative attitude at the LMB."


CREDIT: MRC Laboratory of Molecular Biology
Venki Ramakrishnan with LMB MRC postdocs Israel Sanchez (left) and Hong Jin (right).

Outside those tea breaks, young scientists have easy access to all group leaders, especially their own. None of the leaders have a personal assistant who screens visitors, says Ramakrishnan, whose office leads directly onto his laboratory. "I try to be aware day to day of what's going on in the lab." Voorhees says she sees Ramakrishnan several times a day. "You're more comfortable dropping in and asking a quick question," she says. "At every other lab I've visited, to get to a senior researcher's office, you've got to go through a door, a secretary, and another door."

Big ideas

Another reason for LMB's success may be the risky, hard-to-solve problems the researchers are encouraged to tackle. "At the LMB, you can approach big questions, like how is gene expression controlled?" says Lori Passmore, an LMB group leader studying the function and assembly of protein complexes. Passmore was a postdoc in Ramakrishnan's lab.

LMB researchers can afford to ask big questions: They don't have to teach, and they are free to do whatever research interests them. "There's a tradition of trying to hire smart people and then basically leaving them to it," says Leo James, a group leader in the Protein and Nucleic Acid Chemistry Division. There's less pressure to constantly publish papers. "It's an environment where you're encouraged to go after the big thing instead of having to have a publication every 3 months," James says.


Lori Passmore (CREDIT: MRC Laboratory of Molecular Biology)

Behind the success

LMB's funding model also encourages risky, long-term research and the lab's collaborative culture. It receives stable core funding, which is shared by all research groups and reviewed every 5 years. The divisions each get a share of space and the budget, which they distribute at their discretion, Pelham says. Group leaders can expect a couple of MRC-funded positions for postdoctoral researchers or technicians and an average of two Ph.D. students. Additional postdoctoral researchers may be funded from personal fellowships. Many group leaders also have external grants that allow them to hire more people, but they must get permission before applying to ensure there's enough space for expansion. Research projects are funded from the core MRC budget, subject to decisions by Pelham and the heads of the laboratory's four divisions. The process is faster than making a grant application, James says.

Ramakrishnan says LMB's secure, long-term funding allowed him to focus on his Nobel Prize–winning research, which he began at the University of Utah in Salt Lake City. "I didn't put all my energy into that project until I had the security of the LMB," he says. Otherwise, he'd have spread his efforts over several projects to reduce the risk, and "probably missed the bus."


Leo James (CREDIT: MRC Laboratory of Molecular Biology)

The success of every researcher contributes to the lab's funding prospects, which encourages cooperation, Ramakrishnan says. "One thing I've noticed here is, if someone does well, there's no jealousy. We're all in the same boat."

Replicating success

LMB has a long history, and replicating its culture is a challenge. The Howard Hughes Medical Institute's Janelia Farm Research Campus in Ashburn, Virginia, was founded in 2006 with a similar approach. (See related Science Careers articles here and here.) Janelia Farm even experimented with MRC LMB's traditional English tea and coffee hours, but an all-day cappuccino bar and affordable lunchroom worked better in America, says Kevin Moses, former chief academic officer at Janelia Farm. But whether LMB's culture can be copied remains an open question. Janelia Farm hasn't won a Nobel Prize yet. "The jury is still out," Moses says.

Still, you don't have to be at LMB to profit from its example. "Doing work of high quality and lasting importance is usually a good strategy" for those with high scientific aspirations, Pelham says. "Think of the big questions and try to answer them." Another part of the recipe: "Start small and preferably stay small if you can," Ramakrishnan adds. "If you look at the seminal papers in a big breakthrough and think, 'What was the situation of the scientist when they published this paper?' More often than not, it was when they were small."

The MRC LMB's 13 Nobel laureates (Adapted from the LMB Web site.)

Venki Ramakrishnan

Joint winner of the 2009 chemistry prize with Thomas Steitz and Ada Yonath "for studies of the structure and function of the ribosome."

Sydney Brenner, Robert Horvitz, and John Sulston

Joint winners of the 2002 physiology or medicine prize "for their discoveries concerning genetic regulation of organ development and programmed cell death."

John Walker

Joint winner of the 1997 chemistry prize with Paul Boyer and Jens Skou for his "elucidation of the enzymatic mechanism underlying the synthesis of adenosine triphosphate (ATP)."

César Milstein and Georges Köhler

Joint winners of the 1984 physiology or medicine prize with Niels Jerne "for theories concerning the specificity in development and control of the immune system and the discovery of the principle for production of monoclonal antibodies."

Aaron Klug

Winner of the 1982 chemistry prize "for his development of crystallographic electron microscopy and his structural elucidation of biologically important nucleic acid-protein complexes."

Fred Sanger – twice

Joint winner of the 1980 chemistry prize with Walter Gilbert for his "contributions concerning the determination of base sequences in nucleic acids" and winner of the 1958 chemistry prize "for his work on the structure of proteins, especially that of insulin."

Francis Crick and James Watson

Joint winners of the 1962 physiology or medicine prize with Maurice Wilkins "for their discoveries concerning the molecular structure of nucleic acids and its significance for information transfer in living material."

Max Perutz and John Kendrew

Joint winners of the 1962 chemistry prize "for their studies of the structures of globular proteins."

Vivienne Raper is a freelance journalist in London.

10.1126/science.caredit.a1100063