Talking with ASCB 2015 Keynote Speakers: Biology on Global, Microscopic, and Political Scales
An ASCB Interview in Two Parts
Part One: Jane Lubchenco, Oregon State University
Part Two: Sallie “Penny” Chisholm, MIT
The keynote speakers at ASCB 2015, Jane Lubchenco and Sallie “Penny” Chisholm, illustrate the increasing unhelpfulness of pigeonholes in science. Lubchenco and Chisholm could be lumped together as marine biologists although this would explain little about the science they practice today. True, they both study ocean life, its mechanisms, its evolution to the present, and its worrisome prospects for the future. And they both work at global and microscopic scales. For Lubchenco, a professor at Oregon State University and the former Administrator of the U.S. National Oceanic and Atmospheric Administration (NOAA), her prime subject is a vast near-shore marine ecosystem along the U.S. Pacific Coast. For Chisholm, who is a professor at MIT with a joint appointment in Biology and in Civil and Environmental Engineering, it is a cyanobacterium so tiny that it was dismissed as schmutz by microbiologists for decades. Since its discovery in 1985, Prochlorococcus has turned out to the smallest and most abundant photosynthetic organism on Earth, a significant anchor of the oceanic food chain and, by its abundance and near ubiquitous range around the globe, a key player in the ocean carbon cycle and thus in regulating climate.
You could take the careers of both Lubchenco and Chisholm as indicators of where the biological sciences, on the smallest and largest scales, will be going in the mid-21st century. For Chisholm, it was the world’s smallest photosynthetic organism that turned out to be gigantic. For Lubchenco, it was the highly dynamic, ecologically place-sensitive “rocky intertidal zone” at the ocean’s edge that first pulled her into environmental science and then to defend it, into the politics of science at the highest levels. At ASCB 2015, the two keynoters will talk about what drew them into their science and how cell biology can span their global and micro worlds.
Part Two—Sallie “Penny” Chisholm
Her latest description of her science is “cross-scale systems biology,” and for that, Sallie “Penny” Chisholm offers up Prochlorococcus, the marine cyanobacterium she had a hand in discovering in 1985 and which she has been grooming as a laboratory model system and studying as an extraordinarily diverse wild type. “The beauty of Prochlorococcus is that you can study it both in the lab and in the wild,” Chisholm believes. “You always know where you can find it, find it in great numbers, and find examples of its extraordinary diversity. This makes it possible not only to understand its machinery—how the cell works— but also the planetary forces that shaped that machinery and all of its variants over evolutionary time.”
With Prochlorococcus, she says, “You can study the organism on all scales from the genome or the transcriptome up to the global biosphere. My hope is that it will serve as a model in all facets of an organism, its evolution, its physiology, its ecology, and then its genomic and molecular biology.” Cross-scale biology is not just systems biology in the outdoors, Chisholm contends. “Okay, there’s all that in the cell but the cell is embedded in an environment and an ecosystem.”
Cross-scale systems biologist or marine microbiologist, Chisholm has been crossing scales and disciplines all her career. Take the discovery of Prochlorococcus. The word “discovery” usually sends Chisholm into a paroxysm of professional demurs and credit handoffs to colleagues and collaborators. But it was Chisholm and her former postdoc, Rob Olson, who first put to sea with a flow cytometer. “The key to the discovery was using flow cytometry,” she says. “It’s a standard tool today of cell biology but we were among the first to adapt that tool to study marine phytoplankton, even though that is not what it was designed for.”
Out at sea on an oceanographic survey vessel, Chisholm and Olson were actually studying another larger (1.5μ /microns) cyanobacterium, Synechococcus, which fluoresces an unmistakable orange. But on one cruise Olson noticed red flashes from something even smaller—under 0.8μ /microns. “It’s barely visible through normal light microcopy and even with epifluorescence or phase contrast, you won’t see it unless you know what you’re looking for,” says Chisholm. “If people saw it before, they just thought it was busted up cells.”
It slowly dawned on Chisholm and Olson that the red flashes that kept popping up were not broken bits of something else but a free-living single-cell organism. Going back through the literature, Chisholm realized, “It turns out that it had been discovered two times; once an electron micrograph of it was dismissed as a Synechococcus variant, and another time its tell-tale pigments were thought to be degradation products in seawater. Looking backward and putting all these pieces together, we were able to say this is a different beast.”
And there were a lot of them. Prochlorococcus is so far the most abundant photosynthetic organism on Earth (an estimated 1027 cells total), although Chisholm likes to point out that abundance of organisms increases as size decreases “Prochlorococcus has a lot of superlatives attached to it because of its tiny size.” Still Prochlorococcus has a massive impact on the oceans because of its numbers and because of its near ubiquitous range from 40°N to 40°S. The cyanobacterium produces a unique form of chlorophyll, which once you know what you’re looking for, makes Prochlorococcus relatively easy to measure and to quantify. That makes it easy to estimate what fraction of global ocean photosynthesis is carried out by this single group. And it is large: 10-20%. Thus the “multiplier” is large for the global implications of anything that is learned about Prochlorococcus.
Made by Katherine Huang, Chisholm Lab, MIT.
While Prochloroccus is commonly referred to as a species, its genetic diversity upends classic taxonomic definitions. In a recent paper in Science, the Chisholm lab reported on extensive single-cell genomic studies of Prochlorococcus samples that revealed hundreds of genetically stable—and genetically ancient—subpopulations co-existing within meters of each other, if not within the same drop of seawater. “It changes the way you think about what’s an organism,” says Chisholm. “Prochlorococcus would have been considered a separate species by traditional microbial standards, and yet it embodies enormous genetic and physiological diversity.” So what is a floating mid-ocean Prochlorococcus bloom? “I’d call it a collective or a federation,” Chisholm says.
Living largely in the nutrient-poor tropical and sub-tropical open ocean waters, at different depths and different light levels, these subpopulations appear to stabilize the total population by containing strains adapted to varied conditions. Still Prochlorococcus raises questions, in Chisholm’s mind, about the Darwinian concept of competition as a driver of evolution. “The more we study it, the more I let go of the word, competition. I’m not saying that the Darwinian framework is wrong but is competition really driving and shaping the system? This seems to say that there’s much more to it.” Yet Chisholm shrugs off any notion of a new grand synthesis on her part based on Prochlorococcus. “I don’t have a formal theory for the way we’re thinking about it. We just keep studying it. We leave it to others to use our observations about Prochlorococcus to support the growing belief that nature operates as a finely tuned co-evolved collective, rather than a tooth-and-claw world in which only the ‘fittest’ survive.”
Chisholm does have ambitions for Prochlorococcus. She believes that Prochlorococcus could become a gold standard organism for ecology and evolution in general. “Just as studies of E. coli revolutionized molecular biology, studies of Prochlorococcus—in all its dimensions— could change the way we think about the forces that shape the broader dimensions of life on Earth,” she says.
It’s not an easy organism to culture but the Chisholm lab has developed reliable protocols, keeping clonal strains going for decades at MIT. “It’s a temperamental bug and it’s not fully tamed,” she admits. It doesn’t like being isolated in pure cultures because it has evolved to rely on “co-bacteria,” separate species that are fulfilling certain functions that Prochlorococcus doesn’t do well for itself. Defining these relationships is difficult, she says. It’s not an obligate relationship because Prochlorococcus survives in pure culture. Nor is the relationship symbiotic or parasitic. Mutualistic is the closest term but Chisholm is not happy with that term either. (Indeed this co-dependency led a former Chisholm postdoc, Eric Zinser, and his students now at the University of Tennessee, Knoxville, to develop a new evolutionary theory that they call the Black Queen Hypothesis.)
But there’s an even graver problem. “Here’s the showstopper, “ Chisholm admits. “We can’t do genetics. It won’t take up foreign DNA.” Her lab has worked on manipulating Prochlorococcus genetics for years without success but recently a postdoc with a background in genetics has joined the Chisholm lab. The new postdoc and new gene editing technologies give Chisholm hope. Being able to manipulate Prochlorococcus’ genes would help us address a lot of questions that up till now have eluded us,” she says. “But it will never be like E. coli or lab rats that are easy to grow and grow fast. You have to be interested in new kinds of questions to work with Prochlorococcus.”
Asking new questions requires new models, new methods, and a new mix of disciplines in her lab. “My perspective is definitely ecological but I have designed my lab to include people trained in everything from molecular biology to evolution to oceanography. They are all drawn to working on an organism in context.”
That context is the ocean. Chisholm says the wild side of Prochlorococcus is a huge asset in her lab’s research. “It is the wild microbes that point us in the direction of interesting stories.” For example, nitrate is considered one of the limiting factors for photosynthesis in the oceans, and yet for decades none of the cultures of Prochlorococcus could grow on nitrate as the sole source because they did not have the genes necessary to use it. “We couldn’t believe this was true of all the Prochlorococcus in the ocean so we looked for those genes in pieces of Prochlorococcus DNA isolated from the wild and there they were! That was a strong motivator to isolate strains that are representative of these wild cousins, and we succeeded in doing so. So the answer to the nitrate usage question is, some do and some don’t. Now the big question is ‘Why’?” Chisholm believes that the nitrate story is but one of many that point to the role of diversity in stabilizing the Prochlorococcus “federation” globally.
The lab and the ocean provide checks on each other. “If we only isolated a single strain and studied only that for 20 years, we would have been completely wrong about the ecology and evolution of Prochlorococcus in the oceans,” says Chisholm.
About the Author:
John Fleischman was the ASCB Senior Science Writer from 2000 to 2016. Best unpaid perk of the job? Working with new grad students and Nobel Prize winners.