Hot Team: Berkeley Professor Orchestrates CNS Research

A.L. Harrelson, C.S. Goodman, "Growth cone guidance in insects: fasciclin II is a member of the immunoglobulin superfamily," Science, 242:700-8, 1988. N.H. Patel, E. Martin-Blanco, K.G. Coleman, S.J. Poole, M.C. Ellis, T.B. Kornberg, C.S. Goodman, "Expression of engrailed proteins in arthropods, annelids, and chordates," Cell, 58:955-68, 1989. P.M. Snow, A.J. Bieber, C.S. Goodman, "Fasciclin II: a novel homophilic adhesion molecule in Drosophila," Cell, 59:313-23, 1989. A.J. Bieber, P.M. Snow, M. Hortsch, N.H. Patel, J.R. Jacobs, Z. Traquina, J. Schilling, C.S. Goodman, "Drosophila neuroglian: a member of the immunoglobulin superfamily with extensive homology to the vertebrate neural adhesion molecule L1," Cell, 59:446-60, 1989. M. Mlodzik, Y. Hiromi, U. Weber, C.S. Goodman, G.M. Rubin, "The Drosophila seven-up gene, a member of the steroid receptor gene superfamily, controls photoreceptor cell fates," Cell, 60:211-24, 1990. T. Elkins, K. Zinn, I. McAllister, F.M. Hoffmann, C.S. Goodman, "Genetic analysis of a Drosophila neural cell adhesion molecule: interaction of fasciclin I and Abelson tyrosine kinase mutations," Cell, 60:565-75, 1990. Like musicians in an orchestra, the members of Corey Goodman's laboratory at the University of California, Berkeley, play well together. Their symphonies include occasional solos, but every player is crucial to the overall performance. This group plays the big time. The members of Goodman's lab, using insects as model organisms to study how the central nervous system (CNS) is wired, in the past three years have produced at least six articles identified by the Philadelphia-based Institute for Scientific Information as "hot" papers--garnering an exceptionally high number of citations in a short time. Goodman's team includes a secretary and five technicians, as well as 10 postdocs, six graduate students, and four undergraduates, who have experience in several different subspecialties of biology. Many factors have gone into the evolution and orchestration of this large and successful group, not the least of which is Goodman's conscious effort to think about interactions in the lab. "I encourage people to collaborate and interact and help each other," says Goodman, a professor in UC-Berkeley's department of molecular and cell biology and a Howard Hughes Medical Institute investigator. "But I also try to make sure that everybody has an identity, has something that they're doing that they can really throw themselves into, that they feel is their body of work." Goodman tries to meet with everyone at least weekly--daily when possible--to discuss experiments and look at data. A hand-drawn map of the United States and Europe hangs just outside Goodman's lab. It is dotted with the names of former postdocs and students, a constant reminder of those who have gone before. "Nothing is done in a vacuum," Goodman says. "I can look at things people are doing now and almost see a history of many of the people who have been in the lab. Each one sort of left their imprint on the lab, and each one had a real significance. "The lab continues to grow and continues to change, but it still reflects the influences that they had on people in the lab." In Goodman's early studies of the developing central nervous system, he and his colleagues realized that in most neurons, the pioneering projections called growth cones grow first toward the midline, a row of cells that separates two lateral regions that will produce most of the central nervous system. After crossing the midline, the growth cones suddenly choose a particular longitudinal pathway on the other side. Goodman's group predicted that these cells were expressing one type of molecule on their surface as they headed to the midline, and then switched their expression of molecules when they crossed. At first, Goodman recalls, other researchers found his group's discovery odd "because it was hard to imagine how cells are putting different molecules on different parts of the surface of the same axon. It happens slowly over time, however, and makes a lot of sense." In 1987, when Good-man's team showed this was true, there were skeptics in the field. "Some people said, `Oh, that seems weird; cells switching and having one molecule on one part of their surface and one on another. That must be just some quirk of insects,'" Goodman remembers. But not long afterward, Tom Jessell and Jane Dodd at Columbia University found the same "quirk" in the rat spinal cord. With evidence for the same mechanism in a mammalian system, the disbelievers were converted. Independently, the Goodman and Jessell groups have gone on to identify and study several surface proteins that appear to be involved in the developing neuron's recognition of pathways. Although the Berkeley and Columbia groups do very different kinds of experiments, they continue to point to the fact that there's something very special about the midline of the nervous system that has evolved in both arthropods and chordates, says Goodman. Goodman chooses new lab members carefully, and values the input of the current team in such decisions. "You want people who have the fire in their eyes and who have enough of their own creative ideas, but who realize that interacting with other people is good," he says. "Their lab mates are their friends, and they're not competing with one another." With such a large group, there's almost constantly a provocative finding to ponder, and Goodman is always excited about the latest results. To him, even papers newly accepted for publication are ancient history--interesting, but simply groundwork for the exciting findings of the moment and near future. A paper in Cell last winter (64[4]:801-15, 1991), for example, reports on work by a postdoc in the lab, Christian Kl„mbt, who used a variety of genetic techniques and molecular markers to study the Drosophila nervous system midline. He found that certain midline cells are required to send a signal that causes neural growth cones to head for the midline. Goodman says the paper establishes a model for activity at the midline and has set the stage for a whole body of work that his lab and others will pursue. "This paper taught us that although the midline is just a small number of cells, it is a very special set of cells," says Goodman. "That's true in an insect, and it also seems, from work in the Jessell lab at Columbia, that the midline cells are very special cells in vertebrates as well." Kl„mbt has gone back to Cologne, Germany, where he has taken a position as an assistant professor. But based on what he learned, others in the lab are making random mutations throughout the entire Drosophila genome in search of the genes involved in sending and receiving the signals that draw growth cones to the midline. Goodman is particularly excited about one of the new mutations recently identified by postdoc Mark Seeger and technician Dolores Ferres-Marco. "It's perfect because the cells that give the signal are still there, and on all other accounts they behave normally," Seeger says. "And the cells that would normally grow to the midline are still present, and they're normal except that their growth cones no longer head toward these cells, but they head somewhere else." Goodman hopes to find a small handful of such genes that affect one specific guidance event. Then, using a variety of molecular and genetic tricks and some cell biology, his group will try to determine which are on the sending end and which are on the receiving end. Without the knowledge the Goodman group gained from Kl„mbt's work, they would be unable to carry out some of the screens and analyses they are now doing. By the same token, Kl„mbt's work was built upon the studies of several postdocs and students who preceded him. Members of the Goodman lab recognize the potential hazards of large research teams, but feel their lab overcomes them. "It's big, and some people would consider that a drawback," says fourth-year graduate student David Lin. "But I actually like that because it means that if you ever have a question, there's got to be somebody who knows the answer." Technician Zaida Traquina agrees with Lin. Although the size of the lab makes her responsibility for stocking all supplies for the lab somewhat difficult, she enjoys the variety of personalities. She says that the lab maintains a good balance between being close and keeping professionalism. "There's never a boring moment," says Traquina, whose name has appeared on several of the group's publications. "There's always something new coming up, and I really enjoy that part of the research. If it's not you that discovers something, someone is doing a little discovering themselves, and you really get to share in that." Goodman's lab includes a mix of scientific backgrounds, including genetics, molecular biology, biochemistry, and cell biology. He oversees this diverse activity, much like a conductor who can be successful even though he doesn't know how to play each instrument in his orchestra. "There are things that go on in the lab that I've never done with my own hands," he says. For example, Goodman's earliest work focused on cell biology in grasshoppers, but increasingly his lab is working on Drosophila genetics. "My formal training wasn't in Drosophila genetics," he says. "But I have great people who come to my lab, I have other really good labs around me, and my brain's not so hard-wired--I'm still able to learn those things." Goodman hopes that the interactions are two-way: that those who come to his lab will be influenced by him, but that they will also have an impact on him. "There's one particular geneticist in the lab who came from a very strong Drosophila genetics background," he says. "I always kid him and say that before he leaves the lab, I want him, when he dreams or fantasizes about his experiments, to be thinking about them in terms of cells, and not just in terms of genetic constructs. And of course he takes as his goal that he's going to try to turn me into a geneticist. But that's good." Although he frets that the lab may be spreading itself too thin, Goodman also encourages projects that diverge from the group's main focus on nervous system development. Several years ago a postdoc in his lab, John Kuwada, wondered to what extent vertebrates use some of the same cellular principles the lab had learned about in grasshoppers and flies. Kuwada chose to study a simple vertebrate organism--zebra fish--and has since started his own laboratory at the University of Michigan. "I don't know one end of a fish from another," Goodman says, "but it was fun to be intellectually involved in what John was doing." More recently, Nipam Patel has completed his graduate research, on the evolution of segmentation, in Goodman's lab. His soon-to-be-published findings give exciting insight, says Goodman, into how the pattern of segmentation evolved from primitive to advanced insects and what sort of changes really took place during evolution. In the summer, Patel will set up his own lab at the Carnegie Institution in Baltimore to study that process. "That's not something we're going to continue to study, because it deserves having a whole lab," Goodman says. "But I'm always going to take pride and satisfaction in the fact that it was really fun to be involved with Nipam in the early years. "I want to keep the lab focused on certain things, but it's also fun to have people start up different areas," he adds. "I get vicarious pleasure out of that, whether they continue to work on that area or somebody does. It's been fun to play cheerleader, in a sense, on different [projects]." Inez Drixelius, the lab secretary for eight years, says Goodman has a talent for maintaining a good-spirited group: "In all the years I've been here, there are personalities that clash occasionally, but I think he sort of instinctively knows who's going to fit in and who isn't." Goodman, in turn, credits Drixelius with liberating much of his time. Although officially a secretary, Drixelius is really a lab administrator, taking care of visas, manuscripts, grant applications, postdoc applications, and a variety of editorial responsibilities. "The days I'm happiest are when I come to work not having lots of administrative appointments and when I know that I can spend a big chunk of the day out in the lab," Goodman says. Goodman overcomes some of the hassles inherent in administering the work of big labs by delegating many of the lab chores. Technicians share major responsibilities for overseeing different parts of the lab, and every grad student and postdoc has been assigned a piece of equipment to take care of. "The time I'm in the lab, I can talk to people about experiments," says Goodman. "I'd much rather talk to them about the experiment they're doing than worrying whether the PCR machine is going to get fixed." Goodman no longer has the opportunity to carry out experiments with his own hands. "If I'm spending three or four hours out in the lab, it's high-quality time of really thinking about results and looking at them and trying to analyze them," he says. "Maybe I'm not spending the other four hours pipetting things from one tube to another, but I've paid my dues to that." Even so, sometimes he misses being at the bench. Friends tease him, he says, saying that he uses his hobbies--which include playing the piano, cooking, wine making, and some carpentry--to take out the frustration of wanting to do things with his own hands. "It's as if early on you're the pianist or violinist, and now suddenly you're a conductor," the UC-Berkeley professor says. "It's really fun being a conductor, but every so often you wish that on the side you were able to still just be playing the solo instrument. "There comes a point where I think if you take people into your lab, you have a responsibility to them to spend time with them, talking about what they're doing, trying to advise and guide them. "By choice I've created a lab that in some ways is like an orchestra, and so I have to be the conductor of that. The sacrifice is that I'm not sitting there playing the violin anymore." Laurel Joyce is a freelance science writer based in Palo Alto, Calif.

Hot Team: Berkeley Professor Orchestrates CNS Research

Interested in reading more?

Become a Member of