Katelyn Billings

There was a time when Katelyn Billings considered herself extremely productive if she set up 10 reactions over the course of a day. Now, she says, “Running a few thousand reactions in a day is no longer out of the ordinary.”

Billings achieved this leap in productivity in her role as a chemist leading the design and construction of DNA-encoded libraries for pharmaceutical giant GlaxoSmithKline. DNA-encoded libraries are collections of millions of small molecules, each attached to a short strand of DNA that encodes the instructions for making the small molecule. Those millions of small-molecule-DNA conjugates are tested all at once against a single disease-related protein. Scientists then use the DNA to decipher which compounds bind to the protein target.

DNA-encoded libraries have been around for more than 25 years, but they’re enjoying a resurgence in popularity. That comes in part as drugmakers look to overcome drug targets that have eluded conventional high-throughput screening methods. And Billings and her colleagues have set their sights on creating better, more diverse libraries.

In the 3 years she’s been at GSK, Billings has been involved in the creation of 10 libraries, ranging from 1 million to 225 million compounds. On any given day, she might strategize which reactions or building blocks to use to construct a library, decode the results of a recent screen, or create a new chemical reaction for library building.

“What drew me to DNA-encoded libraries was the ability to impact many different projects,” Billings says. The libraries she makes become the starting point for finding small-molecule drugs for the many diseases, such as cancer and HIV, that GSK wants to tackle.

To expand libraries’ diversity, part of Billings’s job is to translate traditional and cutting-edge organic reactions into transformations that can be done with DNA present. This kind of chemistry requires an organic chemist’s nemesis: water. To that end, Billings recently collaborated with the University of Pennsylvania’s Gary Molander on a project that uses photoredox chemistry to couple sp³-centered radicals to DNA. Billings thinks this approach will be useful for a wide range of building blocks.

“This is really a phenomenal technology,” Molander notes, and Billings, he says, “is probably one of the best people in the world at doing it.”

Billings is also working on a computational approach to help construct better DNA-encoded libraries. She says the goal is to strike a balance between selecting every possible building block and selecting only the small subset of those guaranteed to have good properties.

“She is a superb scientist, and I would point to her flexibility and willingness to take on things that she’s not expert in and really bear down on the toughest of problems with a smile on her face,” says Andrew Phillips, who is CEO of C4 Therapeutics and was Billings’s PhD mentor at Yale University.

Billings credits much of her success to her ability to work with a team. It’s a skill she developed as the pitcher of her high school’s softball team, which won the Vermont state championship her junior and senior years.

“No one person could drive the team forward to success. You really all had to work together and rely on each other,” Billings says. “I think that team-sport mentality translates well to work in industry, where we all have to work together.”