“Hey wake up, we’re going somewhere,” Ye-Jin Eun’s parents announced one Sunday afternoon, initiating her transcontinental journey from her hometown of Gwangju, South Korea to the Department of Molecular and Cellular Biology at Harvard University. To Eun’s surprise, they proceeded to an information session for a high school exchange program in the United States. “I came totally unprepared,” she recalls, “so I borrowed a pen from somebody sitting behind me” in order to pass the qualifying exam and begin her high school education in Minnesota.
Eun, nicknamed “Jenna” by her American host family, attended University of Wisconsin-Madison, where she joined Silvia Cavagnero’s lab as a biochemistry major, researching protein folding mechanisms. Despite the widespread presence of the globin fold in most living organisms, only eukaryotic globins had been employed as model proteins in folding/stability studies at the time. Eun’s work introduced the first thermodynamic and kinetic characterization of a prokaryotic globin, and suggested that the general folding features of bacterial and eukaryotic globins are preserved through evolution while kinetic details differ.
On-track as a pre-med undergrad, Eun believed that becoming a physician would be her best shot at making a palpable, positive impact on society. However, three weeks in Uganda during her senior year and a new role model, Professor James Ntambi, led her to reevaluate that assumption. Ntambi, a biochemistry and nutritional sciences professor, had established a unique study-abroad program in which students complete a semester-long course on international health and nutrition, then travel to Uganda to explore the subject first-hand. As a student in this program, Eun quickly realized, “Yes it’s important to have doctors, yes, it’s important to have drugs, but, ultimately, in order to take drugs you need to have a cup of clean water that you can take them with and if you don’t have that then it’s not as effective.” Eun observed how improved infrastructure and access to preventive health care help individuals emerge from poverty and that higher education and research make it possible to sustain this development. Thus, Eun concluded that she needn’t go into medicine to make a difference, but, like James Ntambi, could contribute to both education and research in the academic arena. So she remained at UW Madision to pursue a PhD in Doug Weibel’s lab.
In the meantime, she joined student-organization-turned non-profit, Village Health Project (VHP), founded by alumni of the Uganda program. Throughout her doctorate, Eun persevered to help VHP improve access to clean water, curb malnutrition, and upgrade educational facilities in a rural Ugandan village.
In the Weibel lab, Eun set out to expand the range of chemical and engineering tools for studying bacterial cell biology. She developed chemical probes to manipulate the intracellular organization of bacterial cells and created physical tools to engineer their growth environment and modulate their interactions with other cells. In collaboration with Martin Thanbichler’s group at the Max Planck Institute for Terrestrial Microbiology, she discovered two compounds, DCAP and divin, from a high-throughput small molecule screen and determined that they perturb the organization of bacterial membranes and cell division.
Additionally, Eun found that DCAP effectively kills nutrient-deprived and biofilm-associated cells. “This makes DCAP attractive as an antibiotic,” she suggests, “since dormant bacteria and biofilms cause persistent infections, and they are difficult to eradicate using antibiotics currently available in the market.” Her results demonstrated that slow-growing bacteria could be efficiently destroyed by targeting their lipid membranes and led to a pending patent application.
In the midst of her doctoral research, Eun attended a summer Physiology Course at the Marine Biological Laboratory (MBL) in Woods Hole, MA, where her interests began to veer away from application-driven research toward investigating basic questions in biology. “One of the key lessons I took away from Physiology,” she reflects, “was that the fusion of biochemistry, microscopy and computational techniques is a powerful approach to quantitatively investigate fundamental biological problems. I realized that I’m interested in how cell shape and size are regulated, and wanted to tackle these questions by using tools from microscopy, biochemistry, and computation.”
In addition to shifting her academic perspective, MBL Physiology introduced her to her current PI, Ethan Garner. Although her first impression was that he was “a bit crazy,” given that he took his tea with five teabags per mug, their research interests coincided, as did the timing in their careers; When Eun and Garner met at an MBL Physiology reunion, Garner was about to embark on his faculty appointment at MCB and Eun was in the market for a postdoctoral position.
Garner was delighted: “When she asked to work with me I told her I’d love to have her, even though I felt as though I was not worthy.” “Jenna brings a complete mash up of different expertise to my lab,” he elaborates. “As a graduate student with Doug Weibel, she worked with chemical biology and microfabrication approaches to studying bacteria. In my lab she is coupling that with new chemical probes, bacterial genetics, advanced imaging approaches, including super-resolution.” At present, “Jenna is cracking open the door to the third, unknown domain of life, looking at the cellular organization and shape development in Archaea. Almost every few months she finds something totally new that we are excited to explore.”
In 2014, Eun earned the Helen Hay Whitney Fellowship and launched into her work with Halobacterium salinarum, a halophilic archaeon found in the Dead Sea. In collaboration with Professors Amy Schmid at Duke University and Ariel Amir at Harvard’s School of Engineering and Applied Sciences, she hopes to determine how these archaeal cells create and maintain their geometric shapes—rectangles, triangles, and other polygons with sharp edges—reminiscent of inorganic materials.
Some evidence suggests that the unique organization of the archaeal cell wall may contribute to sculpting the cell. Unlike bacteria, most archaeal cells have a crystalline array of membrane proteins that cover the entire membrane of the cell. Eun likens these proteins to a sheet of ceramic tiles covering a bathroom floor. Unlike floor tiles, however, these two-dimensional membrane proteins blanket the surface of a three-dimensional cell and therefore suffer defects in their organization. “People have long speculated that the location of defects in the archaeal cell wall may be regulated to control cell growth and division and give rise to the geometrical cell shapes,” says Eun, “but that’s just a model, and we really have no idea how it works. It is astonishing that we have very little knowledge about fundamental processes such as cell wall remodeling and cell division in Archaea.”
Somehow, in her spare time between yoga classes and BSO concerts Eun managed to develop curriculum and secure an American Society for Cell Biology grant for a new Life Sciences Outreach high school workshop on bacterial cell biology. She piloted the program in November and will be teaching it to a fresh batch of AP Biology students this April. Outreach manager Tara Bennett testifies to Eun’s pedagogical chops: “Her analogies were fantastic, making her a master at explaining complex ideas to a young audience with very limited background in microbiology.”
By continuing to research esoteric microbes and volunteer her time, energy, and expertise to educate others, Eun not only satisfies her own conscience and curiosity, but sends a powerful message to those around her that it’s possible to do both. As Garner attests, Eun is “completely fearless in her studies, and always excited to try new approaches [and new] organisms. She is incredibly high energy, and her energy can be infectious.” Doubtless, her energy and ambition will infect and inspire her students this spring and her colleagues and community in future.
