Sarah Ardell Honored with Founding Faculty Award

By Mario Aguilera

A novel method to calculate the risks of drug combinations used in the growing antibiotic resistance crisis has been recognized with an award for outstanding graduate student research.

Sarah Ardell, a third-year UC San Diego School of Biological Sciences PhD candidate, was honored with the 2022-2023 Biological Sciences Founding Faculty Award for Graduate Excellence. Founding Faculty Awards are given each year through an endowment started by some of the first and most influential members of the School of Biological Sciences, which was established in 1960. Founding Faculty Award winner are selected by a committee of emeritus faculty members from the school’s four departments.

Ardell was selected for her research leading to “The population genetics of collateral resistance and sensitivity,” a study published in the journal eLife. The research carries implications for treating antibiotic resistance—a crisis that results in more than 700,000 deaths each year and is now considered one of the world’s most urgent health issues.

Due to rising levels of single-drug resistance, coupled with a lack of development of new antibiotics, doctors are increasingly turning to multi-drug treatments in the hopes that their joint therapeutic effects can stop the evolution of further resistance. But many risks and unknowns are involved in such multi-drug treatments.

Ardell and her advisor, Biological Sciences Associate Professor Sergey Kryazhimskiy, developed a mathematical tool to help doctors calculate the risks of resistance evolution for different drug pairs.

Ardell said she was surprised to learn that antibiotic resistance cannot be thought of as a simple deterministic process. The more she learned the more it became clear that different bacterial populations evolve resistance in different ways, even in controlled lab conditions. The same experiments carried out by different labs often produce contradictory results, she found.

The strain of bacteria, concentration of drugs and the nutrients in the organism’s environment can all lead to a mixed bag of results.

“But even if all of those things are exactly the same you could still get different outcomes in two different iterations just because evolution builds up by random mutations,” Ardell said. “Two different populations could have randomly accumulated different mutations with different collateral effects, even if everything else is equal. There is so much variability and randomness in these processes, which is an incredibly important thing to think about for patients. We want to give drug pairs that we are confident that will, as much as possible, produce collateral sensitivity—and not just 50 percent of the time.”