Many researchers have scientific idols, but Bob Goldstein is one of the few with an actual shrine to his hero. Inside Goldstein’s microscope room at the University of North Carolina, Chapel Hill, there’s a small wall recess dedicated to the cell biology pioneer Ray Rapoport. It was Rapoport, a cytokinesis researcher and professor at Union College for over 30 years, who inspired Goldstein to pursue research, and nudged him toward developmental biology. Today Goldstein is an outside-the-box investigator, a screenprinting and design artist, an eloquent nonfiction writer, esteemed mentor, and more. Goldstein has diverse interests, and serious talent.
“The day I arrived my advisor told me he was leaving.”
As an undergraduate at Union College in Syracuse, NY, Goldstein liked biology’s puzzles, but wasn’t sure they would lead him to a career. Then he had a class with Rapoport. “It was the first time I felt like I knew what scientists did… it was a more creative activity than I imagined,” Goldstein said. Rapoport died in 2010. When the Goldstein lab was renovated a few years ago, he decided to turn an empty fire extinguisher recess into a memorial, enlisting his son to help him paint it. Finally Goldstein installed lights, a picture of Rapoport, and a sand dollar, which was Rapoport’s favorite model organism. It was Rapoport who convinced Goldstein to “try” graduate school. The trial took him to Gary Freeman’s lab at the University of Texas, Austin, where for two years not a single experiment worked for Goldstein. “I wanted to try old-fashioned embryology. I got some worms and started hacking away at the egg cells to try to get the cells out, but they wouldn’t divide. I found that someone had already developed a good culture medium for them—Lois Edgar…. Lois had developed a medium for the cells and methods for getting the egg shell off. She was a research associate in Bill Wood’s lab at University of Colorado, Boulder. I was about to drive from Seattle to Texas, and I asked if could learn from her. It was really very generous of her to do this. I tell her she gave me my career,” he said.
With Edgar’s technique, Goldstein was the first to show cell–cell interactions in the early Caenorhabditis elegans embryo, making a big splash with his first paper.1 “It was surprising because people didn’t think there were many cell interactions going on in the early embryo, and it was surprising because it was happening very quickly, within part of a single cell cycle.”
Goldstein went on to do a postdoc at Cambridge University in the UK with John White, who was one of Sydney Brenner’s first students. “The day I arrived my advisor told me he was leaving,” Goldstein said. White had taken a position at the University of Wisconsin, Madison. Instead of feeling abandoned, Goldstein saw an opportunity. “John left behind all of the equipment, including the original confocal microscope, which he made. I had a lot of independence and a lot of equipment….I started to study cell biological things in C. elegans embryos. One project was how cell interactions can control cell division orientation and what the mitotic spindle looks like.
Another was how the initial asymmetries are developed in the embryo,” Goldstein said. His second postdoc took him to the University of California, Berkeley, and David Weisblat’s lab. It was here that he met his wife, Jennifer, who was working on the same floor. In the Weisblat lab, Goldstein claims he chiefly struggled to make his experiments work and that he started applying for faculty jobs “before my failure became apparent.” His failure was not totally apparent to the University of North Carolina, Chapel Hill, where he joined the faculty in 1999, opening his lab on the same floor as Paul Maddox and Ted Salmon. Jennifer Goldstein, who had trained in genetic counseling before pursuing research, combined her interests and now coordinates research at Duke University on people affected by genetic diseases.
“If you dry [waterbears] out they can survive over a decade, they can survive below a Kelvin, you can heat them above boiling, they can survive the vacuum of outer space.”
Today the Goldstein lab focuses on the cell biology of development with different projects under way on a variety of problems. One group is focused on waterbears (also known as tardigrades or moss piglets), adorable micro- animals with eight legs. “I started working on them as a hobby, trying to find a model closely related to C. elegans, and waterbears presented a big interesting black box in evolution,” Goldstein said. “[They] had characteristics that I wanted, they had small, clear embryos, and they divided pretty quickly. Like C. elegans, we could see what’s going on,” he said. And like in C. elegans, Goldstein can do RNAi knockdowns, a technique developed in his lab.2 It’s not always easy—the waterbear genome has not yet been fully sequenced, and many techniques have not been established for waterbears—but Goldstein sees them as an ideal system for investigating evolution and development, in particular their ability to survive extremes. “If you dry them out they can survive over a decade, they can survive below a Kelvin [−459.67°F], you can heat them above boiling, they can survive the vacuum of outer space,” Goldstein said. “Though when they’re wet you can just squish them and they’re dead,” he admitted.
Nurturing Independent Ideas
Goldstein has an atypical approach to running a lab. “People who work in the lab really come with their own ideas….I feel like the best thing I can do is to take people that have independent ideas and find what is a tractable experiment and what’s not,” Goldstein said.
His students and former students found the Goldstein system refreshing. “Bob created a rich research environment in which we had the freedom to tackle any question that was of interest to us. He always said that he tried to treat his grad students like postdocs, and his postdocs like colleagues, and I believe that he did just that,” said Minna Roh-Johnson, former graduate student in the Goldstein lab and now postdoc at Fred Hutchinson Cancer Research Center.
Cell shape changes are another focus of his lab’s interest, says Goldstein. “That was started by one graduate student, Jen-Yi Lee, who was interested in morphogenesis…..This was a case when I was not encouraging her to do the experiments, but I’m glad she did. So then she set this up where we could find cells going from the surface to the inside of the embryo during gastrulation. There was an interesting cell shape change where the apical side of the cell would shrink to nothing, which would internalize the cell,”3 Goldstein said. Now the lab is screening genes in C. elegans for defects in neural tube closure, which is an apical shape change as well,” he said.
Other Avenues of Communication
Goldstein’s passions outside the lab include literary essays and graphic arts. Goldstein has a solid record of papers on PubMed, but he has also pursued a different kind of writing. Recently Nautilus, a new-age science magazine for the general public, published Goldstein’s riveting account of how Francis Crick and Sydney Brenner were scooped by Marshall Nirenberg in the decoding of the genetic code.4 It was Nirenberg who first published a decoded triplet codon and in the eyes of many contemporaries stole the thunder from Crick’s long-awaited solution to the DNA puzzle. Goldstein said he was “fascinated by this moment when Crick found out about Nirenberg, You can see it as a moral dilemma, and yet Crick’s instinct was to promote Nirenberg.”
Goldstein’s talent for science communication also has a strong graphic dimension. Goldstein designs and screenprints posters for his department’s Distinguished Speaker Series (http://bit.ly/1Je4k1o). The poster idea came to him from local telephone poles. “Chapel Hill has a nice music scene, and I knew there were people making gorgeous concert posters displayed out on telephone poles. I loved these things (screen prints), so I asked if some people would make them. A couple of friends showed me how to do it, so now we have a workshop behind our house,” Goldstein said.
“One thing I find a little bit frustrating about science is that at the end of the day you haven’t made anything. Hopefully you have, but not something tangible often. A paper comes out, it’s satisfying, but I had a neighbor who worked in construction, and every few months there would be a new house. My kids and I have the same urge [to make things], so we end up making things that no one needs,” Goldstein said.
“Every Christmas break we make something. We made a chicken coop a few years ago. This year we made a portrait of Gandhi out of beer bottle caps. Each bottle cap is a pixel,” Goldstein said.
“People who work in the lab really come with their own ideas…”
Goldstein is also famous, at least in Chapel Hill, for his lab parties. As Roh-Johnson recalled, “Once he booked a local bluegrass band to play in the lab, literally, in a bay of the lab, to celebrate the lab’s 10-year anniversary.” Lee, now a microscopy research associate at the University of California, Berkeley, recalls that Goldstein provided an alternative model of a life in science. “Bob not only taught me a lot about science, but also about the importance of having work–life balance,” she said.
1Goldstein B. (1992). Induction of gut in Caenorhabditis elegans embryos. Nature 357, 255–257.
2Tenlen JR, McCaskill S, Goldstein B (2013). RNA interference can be used to disrupt gene function in tardigrades. Dev Genes Evol. 223, 171–181.
3Lee J-Y, Goldstein B (2003). Mechanisms of cell positioning during C. elegans gastrulation. Development 130, 307–320.
4Goldstein B (February 26, 2015). The thrill of defeat: What Francis Crick and Sydney Brenner taught me about being scooped. Nautilus. http://nautil.us/issue/21/information/the-thrill-of-defeat.