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The Lab Report: Developing antiviral compounds and alternatives to radioactive labeling

‘We’re trying to understand what makes proteins special,’ Gellman Group principle investigator says
The+Lab+Report%3A+Developing+antiviral+compounds+and+alternatives+to+radioactive+labeling
Riley Steinbrenner

The Lab Report: Every week, the Lab Report takes a deep dive into the (research) lives of students and professors outside the classroom.

The summer after his freshman year, Kevin Nguyen had a lot to think about. Having just been laid off from a biology research lab he had joined just a few months earlier, he questioned whether a career in science was the right path for him.

“I really wasn’t ready to be in undergraduate research quite yet,” Nguyen said. “I hadn’t really understood how to think like a scientist.”

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In addition to having never taken any college biology courses, Nguyen said he lacked the strategic thinking required to plan out multi-day experiments, experience analyzing data and an understanding of how to approach troubleshooting for experiments that did not go according to plan.

Still, Nguyen said he decided to give both undergraduate research and biology another shot. In the fall of his sophomore year, he started his first set of classes in UW’s rigorous Biocore honors curriculum which is intentionally designed to prepare students for scientific research.

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“What Biocore does is it basically takes you through courses that are all student inquiry based … It forces you to develop skills and to create research questions, how to plan experiments out, how you interpret your results and stuff like that,” Nguyen said. “It’s basically boot camp for scientists.”

Meanwhile, Nguyen also began apply for undergraduate research positions, intentionally searching for groups that communicated their research in accessible, plain language. That semester, he applied to and was accepted into the Gellman Group, an interdisciplinary team of chemists, biologists and materials scientists run by professor at the Department of Chemistry Sam Gellman.

Nguyen said the Biocore curriculum meshed well with being in an actual research lab. As Nguyen toured the multiple simultaneous research projects taking place in the Gellman lab, he also picked up valuable research skills by designing and running his own experiments through the curriculum’s first lab class.

“I think one thing that the Gellman group is advantageous for is there’s so many grad students doing so many different things,” Nguyen said. “When I went to group meetings I got exposure to how people were navigating their projects, how they presented them and how they addressed how to move forward.”

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Broadly speaking, Gellman said his lab group seeks to understand what makes proteins special.

“One thing that that motivates a lot of our research is the recognition that the most complicated chemistry we encounter is biological chemistry,” Gellman said. “Billions of years of evolution have really evoked very complicated molecules that have very sophisticated functions. Usually those sophisticated molecules are proteins, and so we’d like to understand how proteins work.”

According to the Gellman Group website, the group focuses heavily on foldamers, artificial molecular chains that fold into useful structures and mimic protein function. In collaboration with the Columbia University Medical Center, the group is researching the use of foldamers to inhibit virus-to-cell docking mechanisms for Paramyxo- and Pneumoviridae viruses, two viral families which negatively impact human health on a global scale.

In addition, the Gellman group is interested in studying a wide range of topics ranging from cell membrane receptor proteins to novel mechanisms for protein assembly that may shed insight into the origin of life itself.

Gellman said the wide range of topics undergraduates get involved with comes in part from his hands-off mentorship style that encourages students to pursue their own research interests.

“That is a reflection of the fact that I have broad interests and that I am offering students space to make their choices about their own interests,” Gellman said. “I view my job as sort of providing opportunities, ideas, to think about and areas to think about working in, but I want them to be the leaders in deciding what we’re going to do.”

Nguyen’s own research project lies within the Gellman group’s focus on G-protein coupled receptors, a protein embedded in the cell membrane that can pass signals from the outside to the inside of the cell.

Though studying GPCRs is of great interest to researchers — Nguyen said these receptors play a part in the mechanisms of nearly one third of pharmaceutical compounds — observing its activation is tricky and requires radioactive tracers.

Nguyen’s senior honors thesis poses a fluorescent alternative. When activated, his modified GPCRs would emit light.

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Last year, Nguyen’s research won him the Hilldale Research Fellowship. He said his overall experience in the lab has committed him to attending grad school.

While Nguyen secured approval to continue his research in person during the past fall semester, Gellman said he worries the lack of research opportunities available to undergraduates during the pandemic will leave them less prepared and less likely to attend graduate school.

“That is one of the huge tragedies of this process, we can’t take on undergrads … it is hurting undergraduates not to be able to participate experimentally,” Gellman said. “We’re trying to get them engaged in working with us in a virtual fashion, but until next fall, we’re just not going to be able to accommodate any other undergrads in the lab and I feel terrible about it.”

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