Written for the Life Science Institute Magazine (you can read the whole thing here)

Shifting and Sharing Expertise

Amanda Peiffer, a fifth-year graduate student in Anna Mapp’s lab, was one of a small handful of researchers who were permitted to come into the labs throughout the shutdown for essential COVID-related research. Known for studying dynamic transcription proteins, the Mapp lab applied their expertise in targeting challenging proteins to take on a protein called TMPRSS2 — a human protein that helps the SARS-CoV-2 gain access to patients’ cells.

“If your cells are exposed to SARS-CoV-2, TMPRSS2 cleaves the iconic spike protein, ultimately allowing the virus to infect,” Peiffer explains. “If you could prevent that cutting event with a good antiviral drug, you could prevent it from getting into your cells altogether.”

Collaborating with labs across U-M campus, Peiffer and her lab mate Julie Garlick have coaxed E. coli cells to express the TMPRSS2 protein. The researchers are now testing the purified protein against sets of synthetic compounds to find a potential drug candidate, some of this work published in a preprint.

Although the researchers working on this project had permission to come into the labs as needed (following strict safety protocols), the project “started on my couch,” Peiffer says, “just reading a bunch of papers. It’s been really cool to have that turn into a multi-lab project.”

While researching SARS-CoV-2 literature, Peiffer was also focused on rapidly evolving news about the virus. She came across a televised news interview with a respected Chinese virologist, claiming proof the virus was man-made in China and released as a bioweapon.

Peiffer thought that was a very extreme claim to make on a leading cable news network, so she decided to check these claims out for herself to see what kind of evidence the research team had.

The report cited in the interview is a pre-print, a publication that hasn’t gone through the peer-review process. The claim in question cites ten other papers, and the whole work cites 111, which makes the research seem legitimate on the surface, Peiffer says.

“If I wasn’t a trained scientist, I would look at that and believe that it’s a real piece of scientific evidence.”

Digging into the citations, however, she found that many of them are very suspicious: author pseudonyms, research organizations that don’t exist, anti-China corporations and blog articles litter the citations section.

“I thought, there’s something going on here,” Peiffer recalls. So she sent a news tip to CNN, alerting the dangers of promoting the virologists’ claims. CNN took Peiffer’s tip and launched their own investigation, which led to a full report on national TV and on CNN’s website, including interviews with Peiffer and Mapp.  

Vetting pre-prints has been an ongoing challenge, especially when they get picked up in the mainstream news cycle. As scientists continue to rapidly learn more about SARS-CoV-2 research—and about how to efficiently and effectively report the research to the public—Peiffer is thankful that she’s been able to use her growing expertise both to study the virus and to help inform the public about scientific claims. 

Of Mice and Mentorship

While the world waited on more news of reopening or COVID-19 test results, Patrick Sweeney was also waiting for grant scores to come back. Sweeney, a postdoctoral fellow in the Cone lab, had submitted a K99 grant application (designed to transition postdoctoral researchers to a faculty position) in February 2020, just a month ahead of the shutdown. Like the course of events outside of research, all he could do was wait; it was out of his hands.

The Cone lab studies how melanocortin receptors in the brain regulate body weight and food intake. Using mouse models, Sweeney investigates how these receptors specifically impact eating behaviors and emotion.

Researchers who used animals for their research were deemed essential workers; so while he was waiting for his K99 application results, Sweeney was able to come into the lab — but on a very limited basis. The LSI had implemented strict shifts to minimize the number of people in the building at a time, so Sweeney found himself in the building at odd hours to take care of the mice and perform a few approved experiments.

“It required a lot more communication and collaboration between lab members,” Sweeney recalls. “If you can only come into the lab after 3 p.m., that makes time-lapse experiments hard to do, so we had to be more flexible… and people in the lab adapted to it.”

In the blistering humidity of a Michigan August, as U-M was slowly ramping up research activities, Sweeney got the definitive response to his application: he was awarded a K99. Funding in hand, Sweeney started looking for faculty jobs right away and preparing to transition.

The COVID-19 pandemic has devastated the academic job market, with many universities facing budget cuts and hiring freezes. Sweeney, like many, was worried about job prospects during this turbulent time. Fortunately, both he and his fiancé found and accepted positions at University of Illinois, Urbana Champaign.

As he prepares to open his new lab in the fall at UI, Sweeney thinks that (despite its many challenges) the experience of being a researcher during a pandemic and witnessing how his own PI navigated the research ramp-down will help set him up for success as a leader.

Balancing safety requirements with research priorities, considering everyone’s comfort levels, putting researchers’ needs into perspective when making a decision, and delegating tasks are all key leadership traits he’s observed from his mentor and hopes to emulate as a PI himself.

“There will still be a lot of restrictions, and the uncertainty is scary,” Sweeney acknowledges, “but we will do what we can do to make things better.”

Travel – along with research and new starts – Restricted

As Sweeney plans how he’ll start his lab and train students, he hypothesizes that “toughest part has been for the new people” — especially new graduate students and postdoctoral fellows.

Sara Wong, a recent alumus of the Lois Weisman’s lab at the LSI, described the timing of her graduate dissertation defense and postdoctoral job hunting as “perfectly bad.”

Because her defense was planned for early May 2020, the majority of her interviews for postdoctoral positions were scheduled in February and March, as COVID cases surged. For Wong, this raised handfuls of tricky questions. “Should I postpone my defense? Should I just do virtual interviews? What’s going to happen?”

But Wong also knew she couldn’t just wait for answers, so she capitalized on the research ramp-down by using the time out of the lab to finalize her thesis. She successfully defended with family and friends over Zoom, at a time when the platform was still new to most attendees.

Working during a pandemic actually ended up helping Wong make the challenging choice of where to pursue her postdoctoral research. She accepted a position at the University of Utah — not just because it was one place Wong visited before COVID-related travel restrictions canceled most of her in-person interviews, but also because of the less crowded spaces and the rock-climbing opportunities.

 “I was super productive but also really burnt out,” Wong says of her time wrapping up her graduate work. “That experience confirmed the importance of a work-life balance, and access to the outdoors, for me,” Wong explains.

For some, like Sweeney and Wong, travel restrictions impacted their process for moving to the next stage of their careers. But for other researchers, like Yilai Li, such restrictions interrupted all aspects of their everyday life.

Li, a postdoctoral researcher who joined Michael Cianfrocco’s lab at the LSI in late-2018, had not been back to his home in China in five years. In February 2020 he returned to his hometown to visit family, celebrate the Lunar New Year festival, and renew his visa. He didn’t expect to extend his stay almost 15-fold, lasting multiple months rather than weeks.

Within a few days after arriving to China, he realized “[COVID-19] is much more serious than people expected.”

It wasn’t long before the rest of the world realized the seriousness of the developing pandemic, and governments issued travel bans barring international travel. The United States halted travel from China and Europe, the two first big hotspots, and closed the embassy where Li needed to renew his visa.

Early on during his quarantine, Li would stay up until 5 a.m. to watch the COVID-19 press conferences from the U.S. for news about when he could come back to Michigan. Because much of his work at the time was computational, though, he did not let the travel ban slow him down. He continued developing a data processing pipeline for determining the structure of the SARS-Cov-2 spike protein.

Nevertheless, Li was nevertheless eager to get back into lab.

After 10 months and countless exchanges with immigration officers and the American embassy, Li was finally able to return to the United States and begin work on a new project studying the SARS-CoV-2 spike protein.  

“I still feel like the luckiest person in the world,” he says, now back at the bench. A sentiment that researchers in the LSI share now that restrictions are continuously lessened, perhaps returning to normal.