How can an animal virus turn into a human disease? Between the ongoing COVID-19 pandemic and the looming concern of avian flu, the question is an urgent one, and the lab of Tyler Starr, PhD, is looking for answers. Starr, an assistant professor of biochemistry in the Spencer Fox Eccles School of Medicine (SFESOM) at the University of Utah, has just received a prestigious $300,000 Searle Scholar Award to help power his research over the next three years.
“We’re interested in understanding how and why viruses evolve properties that allow them to infect humans,” Starr said, “and we can use that to understand the distribution of viruses out there in nature that could be capable of spillover.” Getting a sense of which viruses could potentially become dangerous is an important part of public health preparedness, Starr added. “If we want to have antibodies or vaccines prepared to prevent a pandemic, they need to span that viral diversity.”
Uncovering hidden risks
In Starr’s work so far, he’s investigated how antibodies against HIV develop, as well as studying the evolution of the SARS family of coronaviruses: a broad group that includes COVID-19 and many of its distant relatives, most of which infect bats. His lab found that one bat virus, which had been considered low-risk by epidemiologists, was only a few mutations away from being able to bind a human protein—a critical step for the virus to be able to infect humans.
While the virus would likely need to change in other ways to be able to cause a fully transmissible human disease, Starr’s discovery suggested that epidemiologists and vaccine designers should keep an eye on a broader swath of viruses than before.
As the lab finalized their results, a similar virus was discovered to indeed be able to bind the human protein.
This kind of fast-paced discovery is not unusual in Starr’s field; compared to other evolutionary models, viral evolution occurs extremely quickly. “It’s dynamic and rapid evolution,” Starr said. “We can do our experiments and literally watch in real time as they help explain what’s happening across the world.”
“Tyler has done groundbreaking work on SARS-CoV-2 viral spike protein evolution and receptor use, and, more generally, on how proteins evolve and how viruses jump from one species to another,” said Wes Sundquist, chair of the Department of Biochemistry in SFESOM. “He is already widely viewed as one of the world leaders in elucidating these fundamental issues that are of critical importance to biology and human health.”
Exploring New Frontiers
Starr will use his Searle Scholar Award to expand his investigations into new families of viruses. With the new funding, his lab is bringing a similar evolutionary perspective to viruses that haven’t caused full-blown pandemics, like the MERS family of coronaviruses, which is even more diverse than SARS. Understanding how these viruses evolve could help researchers design vaccines and antibodies that would be effective in the event of future pandemics. Starr’s lab is also planning to investigate the evolutionary factors that drive viruses to be able to infect humans—the better to understand when and how it might happen again.
The Searle Scholars program supports new faculty who are pursuing especially creative and groundbreaking work. Milan Mrksich, PhD, Scientific Director for the program, said, “Our Scientific Advisory Board has selected 15 outstanding early career scientists, whose work spans a broad range of disciplines in the biological, chemical and engineering sciences, and that have the potential to change the directions of their fields.”
A unique aspect of the award is that it’s not tied to the success of a specific avenue of research, which gives investigators the freedom to explore high-risk, high-reward avenues of research. “It’s an award that lets you have a bit more freedom and flexibility to explore new things,” Starr said. But he added that he’s especially excited by the opportunity to meet other scholars and make new connections.