Tracing Covid-19’s Global Course By Jennifer Meininger Wolfe

In June, a patient in London who was infected with COVID-19 was tested for the virus in a doctor’s office. One week later, a trio of researchers from Ursinus was analyzing the genetic sequences of that same test sample during a COVID-19 boot camp hosted virtually by Rutgers University. The data collected would be used to help trace the virus’s evolution as it traveled around the world.

When Britney Dyszel ’22 received the invitation to join a multi-institutional interdisciplinary research team to investigate the COVID-19 virus in June, she was so excited that she ran throughout her house to share the news with her entire family. There was only one problem: she had a six-week surgical internship that overlapped with the research opportunity that Associate Professor of Biology Rebecca Roberts was offering. “I wanted to do both so badly! I couldn't choose,” said the biochemistry and molecular biology major. Shortly after, COVID-19 chose for her. The surgical internship was canceled due to safety concerns.

“I'm glad things worked out the way they did,” said Dyszel. “Being able to research a novel virus during a pandemic does not happen often.”

The weeklong research experience, a.k.a. boot camp, was designed and directed by members of the Institute for Quantitative Biomedicine at Rutgers University and the RCSB (Research Collaboratory for Structural Bioinformatics) Protein Data Bank. This year the event was funded, in part, by four separate National Science Foundation grants awarded to BASIL (Biochemistry Authentic Scientific Inquiry Lab) Consortium members, one of whom is Roberts.

The pride I felt as I witnessed these two young scientists engage with world experts, ask questions, and make their own discoveries—that’s why I teach!”

Thirty-three students from 11 colleges and universities work in BASIL labs on their campuses to prep for the work at Rutgers. As one of the BASIL mentors, Roberts helped facilitate the daily sessions and was able to invite two students to join the boot camp.

Kailey Martin ’21, also a biochemistry and molecular biology major, attended the event as well. She was eager to “develop a better understanding of what exactly SARS-CoV-2 is and how it’s been able to have such a large global effect.”

She and Dyszel had just wrapped up a course called structural biology with Roberts in the spring. “In that course, we dove deep into why and how proteins do what they do,” said Martin. “We even utilized some of the same protein visualization software that we ended up coming across in boot camp to hypothesize the function of an unknown protein.”

from left to right: Kailey Martin ’21, Britney Dyszel ’22 and professor Rebecca Roberts

Another commonality between the boot camp and the course was the Protein Data Bank (PDB). Dyszel, who says she is fascinated by proteins and how their function is so dependent on their structure, admits she was a bit starstruck. “I still can't believe I was doing research with Stephen K. Burley, the president of the PDB.” The PDB was established in 1971 and boasted more than 150,000 protein structures by 2019. Working not only with a tool that is so significant to researchers and scientists across the country, but also working with the people who make the database possible, felt “completely unreal,” said Dyszel.

“The pride I felt as I witnessed these two young scientists engage with world experts, ask questions and make their own discoveries—that’s why I teach!” said Roberts.

When news of the virus started coming out of Wuhan, China, Roberts was amazed how fast science was able to use the gene sequences and determine the structures of some of the viral proteins. “Even back in February, I was sharing information about the structures with my students. These structures were all being deposited and distributed through the Protein Data Bank,” she said.

With every piece of data found, and every step forward that we took, I felt more and more hopeful that one day a small molecule drug or vaccine will be made … This boot camp showed me that every day researchers are getting closer to beating COVID-19.”

At the boot camp, the focus was first on learning about SARS-CoV-2: its evolution, origin, structure and method of transmission. The focus then shifted to learning to use the bioinformatics tools, which are computer-based tools that display the three-dimensional shape of an enzyme in the virus. Using samples from COVID-19 tests taken from around the world, the researchers analyzed actual sequences of the virus.

“As the virus replicates, it can also mutate,” said Roberts. “Many of the mutations don’t really do much at all, but others might. It’s important to start to understand which mutations are popping up and which ones are sticking around because the enzyme we looked at is a potential target for an antiviral drug. We want to know all of the possible shapes it can have since mutations may alter the shape slightly.”

There were roughly 160 known mutations at the time of the boot camp, according to Dyszel. With molecular visualization tools such as PyRosetta, FoldIT and the PDB, the group successfully tracked all 160 mutations and pinpointed them in the protein structure of Nsp5.

For Martin, seeing researchers from across the country come together at the boot camp made her excited for her future as a biochemist. “It inspired me to continue on my path to become part of my own research team,” she said. “It opened my mind up to the thought that, maybe one day, I could be on the other end of the screen teaching a younger generation about the epic COVID-19 pandemic.”

Seeing science move so quickly—and be part of it, such as working with samples that had come out of London the week prior—was something Roberts found exhilarating. “We were looking at something that someone the week before had been tested for in the doctor’s office,” she said. “It was surreal in a way. I felt a bit more in control during a time when everyone is feeling powerless.”

Dyszel agreed. “When the pandemic began, I was initially very stressed and worried,” she said. Completing the boot camp made her feel more relieved—empowered even—as she learned more about the protease responsible for the pandemic. “With every piece of data found, and every step forward that we took, I felt more and more hopeful that one day a small molecule drug or vaccine will be made,” she said. “This boot camp showed me that every day researchers are getting closer to beating COVID-19.”

When did you realize that COVID-19 would have a significant impact in the U.S.?

DR. REBECCA ROBERTS: “I think at the start of March, as we were moving into spring break. Ursinus students and my own children were still in school. I had some travel planned to attend a conference in California in April, and I was deciding whether to attend, as it required airplane travel. I was also supposed to bring several students to a conference in Philadelphia at the end of March to present their research. I told them I would support whatever decision they made in terms of attending the event. I think that is when I realized that life in the U.S. and everywhere was really going to change. Both conferences ultimately moved to fully virtual formats, so the decision was made for all of us.”

BRITNEY DYSZEL ’22: “Back in March, I didn't think COVID would become so significant to the United States. Ursinus had just ended for spring break, and I expected to go back. Halfway through spring break, we were told that classes would resume a week later than normal. At that point, I still was not that convinced, or maybe I was in denial. The moment I got the email saying we would not return at all that semester is when I realized the impact COVID-19 was going to have on the United States. I thought everything would resolve by May or June because most viruses are seasonal, but here we are in the fall and COVID-19 is still devastating the globe. As unfortunate and scary as that is, I know that countless research teams, universities and companies across the world are working toward a treatment every day. The COVID-19 boot camp proved this to me.”

KAILEY MARTIN ’21: “It’s a moment I’ll never forget. Our softball team was is Florida for spring training in March, and after playing two games in the morning, we boarded the bus and our coach told us that our season was suspended. None of us ever thought it would happen to us. It was one of those things that keeps happening to other people, but you think, ‘No, that’s never going to happen to me’—until it does. Playing on that team was one of the best experiences I’ve ever had in my life, and we played our hearts out in each and every one of the games we had that week. It was such a sobering experience hearing that it was all taken away in an instant, but it serves as a reminder to live life to the fullest each and every day.”

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