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Profile of Susan S. Golden PROFILE Profile of Susan S. Golden Sujata Gupta Science Writer Susan Golden did not set out to become Golden pursued other passions. She loved an expert in biological clocks, the internal literature, she says, an interest gleaned timepieces that keep life on Earth adjusted from her mother, an avid reader. And she to a 24-hour cycle. Instead, Golden, elected played the bassoon in the school band— in 2010 to the National Academy of Sci- where she made most of her friends. “That ences, wanted to identify the genes that un- turned out to be a social bifurcation. I did derpin photosynthesis. However, her focus not realize that the band route is the nerd changed in 1986 with the discovery of route. You can’t break over into the other biological clocks in cyanobacteria (1). [cool] group,” Golden says. She also worked Because cyanobacteria are among Earth’s on the school newspaper as a photographer, earliest living organisms, the discovery made one, she is quick to note, without any formal clear that biological clocks are evolutionarily training. By the time she graduated high ancient. Golden had been studying photosyn- school in 1976 as salutatorian of her 600- thesis in cyanobacteria since graduate school. student class, Golden harbored dreams of Her reason was simple: Cyanobacteria are becoming a photojournalist for Life maga- single-celled, and thus they are much easier zine or National Geographic. to manipulate in a laboratory than plants. Golden’s main consideration in selecting a With her expertise in cyanobacteria, Golden college, though, was not prestige or program found herself well-positioned to identify the of study but money. By this point, Golden’s genes and proteins that make the clock tick. parents were divorced and her mother “Cyanobacteria are present in niches and shouldered her expenses. “When I found Susan S. Golden. habitats all over the planet,” she says. out how much my mother made, I was “They’re very good at adapting to their shocked by how poor we were,” Golden habitat and that adaptation involves doing says. So when Mississippi University for wanted to perform molecular biology re- things at the right time.” Their timekeeping Women in Columbus offered her a place, search. So Golden joined the laboratory ability, she adds, helps cyanobacteria gen- Golden welcomed the opportunity. How- of Lou Sherman, who had earlier invited erate about 30% of atmospheric oxygen. ever, after only a day of classes, Golden her to enter UMC. Over the years, Golden and her collabo- realized that she didn’t want to be a jour- Besides providing her with academic focus, rators have revealed that the clock in cyano- nalist. Instead, Golden found herself loving graduate school brought Golden another surprise: a husband. James Golden, another bacteria works like a mechanical clock, introductory biology and soon switched her ’ complete with oscillators, gears, and hands. major to biology with a minor in chemistry. NIH trainee, soon became Golden srole In her recent research, including her In- With several advanced placement credits model. Despite decades of running adja- augural Article, Golden has shown how from high school and packed course loads cent laboratories, only recently have their clock proteins interact to synchronize the in college, Golden graduated from college lines of research converged. When they internal clock with the external 24-hour in just 2 years, unsure of her future. For- moved to the University of California at cycle (2, 3). To Golden’s own surprise, this tunately, she was accepted into a PhD San Diego in 2008, says Golden, their lab- recent line of inquiry has taken her back to program at the University of Missouri- oratories joined forces in researching cya- fi ’ nobacteria’s potential as a biofuel. her roots in photosynthesis. Her ndings Columbia. She became one of the school s ’ ’ show that cyanobacteria don’t use sensory first trainees in a new cell and molecular In Sherman s laboratory, Golden scharge was to develop a genetic system that could be photoreceptors, proteins that convey light- biology training program funded by the fi related information into the body in mam- National Institutes of Health. used to nd the proteins that make up the mals, to set their clocks. Instead, cyanobacteria photosynthetic reaction center in cyano- bacteria. The approach relied on a strategy integrate the ability to tell time with their For the Love of Chloroplasts photosynthetic apparatus. In retrospect, says of identifying mutant photosynthesis pro- fi As an undergraduate student, Golden had teins that cause cells to become resistant to Golden, this nding makes sense: In the pro- eagerly followed a once-fervent debate about karyote’sworld,shesays,“If photosynthesis is herbicides like atrazine (5). Golden con- ’ whether or not to allow recombinant DNA tinued the work when she entered Robert running, the lights are on. It s daytime. If research to continue. Despite the potential ’ photosynthesis is not running, it’s dark.” Haselkorn s laboratory at the University to fundamentally alter the course of genetic of Chicago in Illinois in 1983. By then, research, many researchers feared that An Unlikely Path to the Academy genetic engineering could inadvertently fi ’ This is a Pro le of a recently elected member of the National The roots of Golden s career in plant biology change innocuous microbes into pathogens Academy of Sciences to accompany the member’s Inaugural Article were not formed at an early age. Instead, (4). At Missouri, Golden realized that she on page 17765 in issue 44 of volume 109. 8758–8760 | PNAS | May 28, 2013 | vol. 110 | no. 22 www.pnas.org/cgi/doi/10.1073/pnas.1305064110 Downloaded by guest on October 1, 2021 PROFILE researchers had isolated the gene thought Golden’s work caught the attention of Carl to a 24-hour cycle? Ultimately, the work to be responsible for herbicide resistance, Johnson, a circadian rhythm researcher at led to Golden’s suite of findings detailing but they could not genetically engineer chlo- Vanderbilt University in Nashville, Ten- how the clock and photosynthesis are in- roplasts to confirm their theory. Golden, nessee. Johnson wanted to know whether tertwined in cyanobacteria. however, was able to mutate the suspected Golden had ever studied circadian rhythms Golden knew that she could change time gene, psbA, and reinsert it into cyanobac- in cyanobacteria. Golden recalled that a zones in her cyanobacteria by exposing them teria. She then exposed the mutants to the graduate student of hers had noticed to constant light, followed by a pulse of herbicide and, sure enough, they withstood “funny oscillations” in gene expression of darkness. However, when Golden mutated the assault. “We could show ... that this re- cyanobacteria grown for several days. “We a gene called cikA, the dark pulse caused no ally is the herbicide resistance gene,” Golden might have actually seen some evidence of change (13). “If you don’t have CikA, you says (6). that,” Golden informed Johnson. She sent still have a pretty good clock, but you can’t The findings demonstrated that genetic him a strain of the luciferase-tagged cya- reset it,” Golden says. “The cells have per- manipulation is easy in cyanobacteria, mak- nobacteria, and Johnson, together with manent jet lag.” ing it a suitable model organism. During her Takao Kondo, a researcher now at Nagoya Next, Golden analyzed the structure of postdoctoral fellowship in Chicago, when she University in Japan, observed biolumines- CikA, revealing that CikA contained a began studying gene regulation, Golden cence from the cyanobacteria increase protein domain that resembled another found that cyanobacteria housed a family during the day and drop at night. The domain in KaiA (14, 15). Golden realized of three psbA genes (7). The three genes cyanobacteria’s light production continued that KaiA might also play a fundamental coded for two forms of the protein, one to oscillate even outside the day-night cy- role in setting the clock. Golden found that mutated to confer resistance to the cle. The researchers were ecstatic. At first, that CikA and KaiA bind to quinones, mol- herbicide, and two that seemed to code for Golden failed to understand the excitement. ecules that carry electrons. In photosynthesis, the same protein. Why, Golden wondered, It didn’t take long, though, for Golden quinones have few electrons (oxidized) when did cyanobacteria house those redundant to become enamored of the world of cir- the lights are off but gain electrons (reduced) genes? Over the next several years her re- cadian biology. Johnson and Kondo ex- when the lights come on. Golden showed search group found that the genes encoding plained that they had fashioned the first that the redox state of quinones influences one form of the protein were expressed known bacterial system in which they KaiA activity: When oxidized, as is the only under high luminance and the other couldisolateandstudythecomponents case when cells go into the dark, KaiA dis- expressed only under low luminance (8). of the clock. The team published their lodges from KaiC—the master protein of Further analysis revealed that cells optimize findings in 1993, noting that the discovery the clock—and binds quinones, thus re- their physiology by using the more efficient of the clock in a prokaryote could explain setting the clock. The clock behaves “just as version of the protein under low stress con- how biological clocks evolved (9). if you hit a light switch,” Golden says (2, 3). ditions and switching to the high-stress op- The three laboratories, joined by Masahiro The finding, laid out in Golden’sInaugural tion when conditions become unfavorable. Ishiura in Japan, began working together to Article, expands an earlier finding show- identify components of the clock.
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