Listening to Bacteria- page 3 | 40th Anniversary | Smithsonian
"Bacteria can talk to each other," says Bonnie Bassler. "Not only can they talk, but they are multilingual." And she knows how to speak their languages. (Richard Schulman)

Listening to Bacteria

By studying microbial communications, Bonnie Bassler has come up with new ways to treat disease

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(Continued from page 2)

Bassler assigns a time and place to the beginning of the great part of her life: the day of a lecture in graduate school when she first learned about the bobtail squid and its amazing bacteria-colored dream cloak. The squid lives off the coast of Hawaii and spends its days safely buried in the sand, emerging at night to hunt. It hovers near the surface of the water and waits for food, such as brine shrimp, to pass by. To avoid casting a shadow that would blow its cover, the squid uses a little trick. Under its protective outer sheath, or mantle, are lobes bulging with bioluminescent bacteria, billions and billions of Vibrio fischeri chemically glowing a cool cobalt blue. The squid can sense how much moonlight is hitting it, and it adjusts apertures on its glowing lobes accordingly. With light from above and below balanced, the squid can hunt shadow-free. The squid gets camouflage, the bacteria get shelter and nutrients, and scientists like Bassler get a magnificent system to ply, one where the “aha!” light bulb is more than a metaphor.

Through studying V. fischeri, researchers learned about bacterial sociability. They found that the bacteria would luminesce only when they were in a crowd, packed together, and would desist from glowing should they float away from their fellows in the lonely dilution of the sea. The researchers isolated the molecule that allowed the bacteria to keep track of one another; they called it an autoinducer.

After earning her doctorate in biochemistry at Johns Hopkins University, Bassler worked as a postdoctoral fellow at the Agouron Institute, a research foundation in La Jolla. While there she fell hard for blinking squid and other lanterns of the sea. She studied V. fischeri and moved on to a related species called Vibrio harveyi. She liked the ease of manipulating bacteria, how she could make mutants, push genes around, cross and backcross strains. She especially liked that her weird luminous workhorses would glow if she did the right thing but not if the experiment flopped, a visible indicator that her research team still takes advantage of today. “If you can turn off the light switch in my lab,” Bassler says, “you’re good.”

It was while studying V. harveyi that Bassler helped make a couple of key discoveries: first, that V. harveyi had its own, chemically distinct version of an autoinducer, a members-only signal for keeping track of local V. harveyi numbers; second, that both V. harveyi and V. fischeri secreted and responded to another sort of molecule. This molecule was able to get a rise out of V. harveyi and V. fischeri alike, regardless of its source. Bassler had stumbled on her bacterial Esperanto. She dubbed the molecule autoinducer 2, and pretty soon she was finding it in virtually every bacteria species she tested: in shigella, salmonella, E. coli and Yersinia pestis, the bearer of plague.

Bassler and her colleagues have examined the molecule in atomic detail and seen what it looks like when it is clasped by its appropriate sensory protein—the “ear” that allows bacterial cells to hear the molecule’s cry. They have begun charting precisely how different species of bacteria respond to the universal signal when it is delivered either alone or in combination with other quorum-sensing molecules. They have shown, for example, that when cholera bacteria receive a mix of the private cholera-only signals and the shared we’re-all-bacteria-in-this-together signal, the cholera microbes become extremely virulent. They have found that the common-language molecules are micromanaged by cellular busybodies called small RNAs. They have found that the system is...complicated. “It’s fun, but it’s hard,” says Bassler. “And that’s good, because I need the job.”

Most interesting people have their share of contradictions, but Bonnie Bassler is like a Greek diner menu of contradictions: every time you think you’ve reached the end, you unstick another page of options. She is proud. She is humble. She is impatient. She’s a saint. She has a coffee cup that says “Diva,” but she freely shares her insecurities. “I’m so worried that my star is falling, that I’ll run out of juice.” She jokes about being bored and wanting to go home, but to anyone who works with her she is a perpetual anti-boredom machine.

“Her enthusiasm is very contagious, and it’s always contagious,” says graduate student Carey Nadell. “After the first few conversations we had, when she’d get me excited about the science, I thought the effect would wear off, the way it does with most things. But that hasn’t happened. I always become happier about doing the science after talking with her.” That cheerleader spirit is not limited to science. Monday through Friday, Bassler is up by 5:40 a.m. and goes to the local YMCA, where she teaches aerobics for an hour. “It’s a very challenging class,” says Jean Schwarzbauer, a Princeton molecular biologist who is one of Bassler’s closest friends and a fellow gym rat. “People come thinking aerobics is something to work up to, but she gives you a day to get used to it and then she starts yelling—in a friendly way—if you’re not working hard enough.” Customers come back for more. “You see a lot of the same people over and over,” says Schwarzbauer. “She calls it a cult.”

Some of her scientific peers have complained that Bassler sometimes hogs the spotlight. “I think she’s a very talented scientist and I’ve promoted her career,” says Peter Greenberg, who studies quorum sensing at the University of Washington. He added, however, that Bassler can have “a tough time” giving others credit. Bassler admits that she’s a “ham” and that she’s glad her last name begins with B so that she’s at the top of her department’s Web page. Yet she is also a zealous collaborator, forever seeking new people to work with: chemists, physicists, X-ray crystallographers, structural biologists, mathematicians, evolutionary theorists. She met a condensed-matter physicist while standing around the baggage claim at a Mexican airport, and the next thing you knew she was collaborating with him. A student in Bassler’s lab named Julie Semmelhack happened to mention to her father, Marty Semmelhack, that she’d been working on an interesting molecule in the lab. The father, a chemist, instantly recognized the structural profile of the molecule—“It’s a furanone!”—so of course Bassler had to work with him, too.

“Working with Bonnie has convinced me that under the right circumstances and with the right people, collaboration can be more rewarding than working for yourself,” says Frederick Hughson, a molecular biologist at Princeton who studies the structure of proteins and other molecules.

Scientists of Bassler’s caliber often have 50 or 60 people working for them, all vying for attention and hot projects. Bassler has 15 or 16 people in her lab, and she prides herself on picking her protégés well. “Only two people haven’t worked out in all these years,” she says. Her requirements are simple. If you want to work in her lab, if you want to be part of the Bonnie Bassler “brand,” as she puts it, you must be extremely ambitious, self-motivated, smart, tenacious, handy with a pipette and not a jerk. “My group selects for a certain kind of person, and that person tends to be really, really nice,” she says. “After all, they’re the ones who will be working with them elbow to elbow for five years, and they notice these things.” A candidate visits the lab, and members tell Bassler what they think. “It’s quorum sensing,” she says.

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