Dr. Tyler Starr has been named a 2019 Damon Runyon Postdoctoral Fellow. He is among 15 new Fellows to receive this prestigious, four-year award. The Fred Hutchinson Cancer Research Center postdoc, who is co-mentored by Hutch computational biologists Drs. Jesse Bloom and Erick Matsen, will study how DNA mutations affect the function of antibodies, a type of specialized immune protein, during the course of an immune response. He hopes his insights will help researchers to design better vaccines and improve antibody-based therapeutics for diseases ranging from HIV to cancer.
“We’d like to not only understand how antibodies evolved or developed, but we would also like to know how to guide their development,” Starr said.
Starr’s background is in protein evolution; he studies how changes in gene sequence lead to changes in protein form and function over millions of years. During immune responses, antibodies undergo a similar process in fast-forward. Though our bodies generally try to stave off DNA mutation (due to downsides like cancer), the DNA code of our antibody genes specifically allows for rapid gene- sequence changes.
Antibodies bind threats, whether from a virus or a tumor, and help block them. During an infection, antibodies make changes to their genes to become better at binding their targets and better at protecting us. Vaccines take advantage of this natural process, called affinity maturation, to generate enhanced antibodies that are better able to prevent infection when we finally encounter the microbe.
“We can now watch that process unfold by sampling someone’s blood, sequencing their antibody repertoire, identifying [antibody] families, and seeing how they changed over time using phylogenetic approaches,” Starr said.
He aims to shed more light on how specific mutations affect antibody function by systematically mutating antibodies and assessing the functional effects of each. Starr will focus on a major type of antibody against HIV that can neutralize a wide swath of HIV variants — exactly the sort of antibody that HIV vaccine developers hope to someday produce.
“We’re trying to survey the landscape of what are the possible mutation effects to some of these key antibodies and see how that relates to what we saw actually happened in their affinity maturation trajectories,” Starr said.
His work will shed light on the forces that shape antibodies during affinity maturation. Understanding these forces could help vaccine designers devise vaccines that guide antibodies along a chosen evolutionary path. Starr’s results may also help answer a long-standing question in HIV research: Why do broadly neutralizing antibodies, which can block infection from a wide variety of HIV strains, take several years to develop after infection? Answering this question could also help researchers figure out how to speed up this process.
The Damon Runyon Fellowship will enable Starr to chart a research path that draws on the expertise of his mentors while heading in a new direction.
“Having your own funding makes it easier to have the independence to work on your own project,” he said.
Sabrina Richards, a staff writer at Fred Hutchinson Cancer Center, has written about scientific research and the environment for The Scientist and OnEarth Magazine. She has a PhD in immunology from the University of Washington, an MA in journalism and an advanced certificate from the Science, Health and Environmental Reporting Program at New York University. Reach her at srichar2@fredhutch.org.
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