Three Seattle scientists who have been studying the coronavirus have been selected among hundreds for national biomedical funding that offers millions of dollars toward their research, positioning them for possible scientific breakthroughs down the road.
Trevor Bedford, Frederick Matsen IV and David Veesler are among 33 researchers recognized this year by the Howard Hughes Medical Institute (HHMI), the largest private biomedical research institution in the nation. The Maryland-based nonprofit is awarding the group of scientists with $300 million — about $9 million per person — to “chase their wildest scientific ideas,” the institute said on Thursday.
The funding will last seven years, though it can be renewed at the end of that period, said David Clapham, HHMI’s vice president and chief scientific officer.
“Science benefits greatly from stable funding,” Clapham said in an interview. “Most scientific projects take many years, sometimes a lifetime, to understand. Hughes provides that sort of stability — enough funding where you’re not just writing grants all the time.”
He added, “We want to free them up so they can really think about what they’re interested in and get to the root of it.”
While the interests of this year’s 33 “investigators” range from brain electricity in mental health disorders to cures for cancer, Bedford, Matsen and Veesler are focusing on viral outbreaks, including SARS-CoV-2, the virus that causes COVID-19.
“These three really stood out,” Clapham said.
Bedford, a computational biologist at Fred Hutchinson Cancer Research Center, became well-known in the Seattle area early in the pandemic for detecting the coronavirus outbreak locally. He’s long been analyzing outbreaks and developing surveillance networks, such as the Seattle Flu Study, an effort led by the Brotman Baty Institute for Precision Medicine, UW Medicine, “The Hutch” and Seattle Children’s.
When Bedford joined The Hutch in 2013, he was working on influenza research and flu evolution, eventually helping launch Nextstrain, an open-source project that analyzes pathogen genome data. Through Nextstrain, Bedford later pivoted to tracking other viral diseases, like Ebola and Zika.
Since the pandemic started, however, he’s been focusing on understanding the virus’ transmission, using genome sequence data to help epidemiologists track local outbreaks, as well as global spread.
“I noticed inklings on Twitter from Wuhan at the very beginning of January,” Bedford said. The first SARS-CoV-2 genome data became available mid-January, and a few days later, “it became clear to me what sort of situation we were in,” he said.
“It was basically an emergency crisis where it was like, ‘I need to alert everyone I know up and down public health what’s going on,'” he said. Later on in February 2020, a day or so after testing samples collected from the Seattle Flu Study, he and his team detected one of the first COVID-19 community cases.
“[The Flu Study] was designed around a pandemic early-warning system, where the key idea was that you can’t just have something that turns on in the case of a pandemic,” he said. “You want a surveillance system that’s responding to seasonal respiratory virus. … But I definitely did not think or have foresight that this would [detect] a once-in-a-hundred-years pandemic in year two of a study like this.”
Tracking viruses with algorithms
Matsen, another HHMI investigator announced Thursday, joined The Hutch in 2010 and uses data to track virus sequences, as well as how immune systems produce antibodies to fend off pathogens.
He’s long been interested in the mathematical and statistical aspects of inferring phylogenetic trees, a diagram that shows how different species evolve based on comparisons in their physical or genetic characteristics. It’s a tool that’s been useful for understanding how SARS-CoV-2 has evolved and spread, he said.
Now, he’s hoping to develop next-generation algorithms for something called Bayesian phylogenetics — where he’ll find a group of trees, or diagrams, that credibly explain data, as well as their probabilities of being correct. This approach could speed up the tracking of a virus’s evolution.
“We are limited significantly in what we do for all this tracking, etc. based upon these algorithms,” Bedford said of his colleague’s work. “So Erick is building better algorithms.”
Matsen and his team are starting from scratch.
“We’re trying a totally different approach,” he said, explaining how his methods use optimization — a quicker way of trying to find the best estimate for analyzing data — instead of sampling, a process that tests a random modification and then decides if the modification is worth keeping.
Eventually, Matsen said, he wants to work with Bedford to deploy a new, real-time system of analyzing viruses.
The process takes a long time, he said, which is why being selected as an HHMI investigator is “perfect.”
Veesler, who runs the Veesler Lab at the University of Washington, has a goal of eradicating infectious diseases in people by mining bat viruses and the immune responses they elicit to combat future viral outbreaks.
His lab has been studying coronaviruses for seven years now. It largely focuses on studying how viruses enter host cells, how they evolve and how the immune system responds. The work focuses on surface glycoproteins, which are involved in virus entry into cells and the targets of neutralizing antibodies.
“I’ve really seen how my world at work that was all coronavirus all the time has become everybody’s world,” Veesler said.
While Veesler dived into understanding immune response in COVID-19-positive people through discovery and characterization of antibodies, he and his lab were simultaneously looking at designing a vaccine “using an approach completely different from the one Big Pharma followed,” he said.
Pharmaceutical companies like Pfizer and Moderna are using mRNA vaccines, which Veesler says are “fantastic” and “really fast,” but manufacturing these vaccines at a scale meeting the global need has proven challenging.
“We have a large part of the world population that is still not vaccinated,” Veesler said.
The vaccine Veesler and his team have been working on, however, is based on a computationally designed self-assembling protein nanoparticle that roughly resembles the coronavirus — a characteristic that may contribute to its enhanced recognition by the immune system. The vaccine remains stable at room temperature for weeks and is currently in Phase 3, the last phase, of clinical trials, Veesler said.
“The Hughes funding will allow us to continue our fight in the pandemic against SARS-CoV-2, but we also want to take a few steps back and look at humans and bats and specifically how viruses are transmitted,” he said. “We need to understand which viruses are worrisome, and how we can inspire ourselves from what we learn to be prepared.”
Veesler added that part of his excitement about the news comes from the new freedom to “take even more risks.”
“That’s not always easy to do with other sources of funding,” he said. “It will allow our science to be even bolder than it was before.”
The three will join the growing group of HHMI investigators in Seattle, including The Hutch’s Jesse Bloom, previously the most recent Seattleite to be selected as an HHMI investigator in 2018.
“We hope they discover great things,” Clapham said.