Making Epistasis Fun

With some basic ingredients – including common yeast, a few test tubes, and notebooks – Dr. Maitreya Dunham’s broader impacts project has not only created research experiences for high school students – the work has also yielded new findings on specific interactions between genes (epistasis) that influence yeast resistance to azoles. Azoles are a class of synthetic anti-fungal compounds that inhibit the growth of yeasts and fungi, including those that affect foods and health.

The student-run experiments are a component of a collaborative project between Dunham and co-investigator Dr. Paul Rowley (“Collaborative Research: Eukaryotic virus-host interaction and evolution in Saccharomyces yeasts” (NSF award #1817816)). The students grow common yeast (S. cerevisiae) in a media containing an azole known to inhibit yeast growth. Successive generations of the most successful yeast are transferred to media with increasingly greater levels of azole. Students track the progression and return the final yeast cultures to Dr. Dunham’s lab for genetic sequencing. After the yeast’s genomes are sequenced, Dunham and her team return the results to the school and students research the mutations as part of their classwork.

The research enables students to observe how mutations in specific genes interact, and how correlated mutations lead to different changes in azole resistance. When the interactions are not additive, but are either greater or less than expected, it’s known as epistasis.

Pigmented yeast makes the research competitive and the experiments more visually exciting. In “yeast fights,” students observe the growth of differently colored yeasts to track which strains are more drug resistant. The colored yeasts come from the lab of Dr. Jef Boeke, also an MCB-funded researcher, and are developed by research assistants “playing” with yeast in their spare time. Some high school students call these colonies their “yeast babies” and, Dunham says, the students are excited to learn what genetic mutations are present in the final yeast colony.

The project itself has evolved, enabling the experiments to persist despite school closings caused by the COVID-19 pandemic. yEvo.org includes a step-by-step protocol and a form for requesting more information on how to participate.

Other collaborators include Dr. Ryan Skophammer, a biology teacher at Westridge School for Girls in Pasadena, CA, who initiated the idea by asking Dunham for a “real” science project for his class; Dr. Bryce Taylor, a yeast geneticist in Dunham’s lab who provides the genetic sequencing; and three undergraduate students. Rowley, the project’s co-investigator, runs yEvo labs in schools local to him in Idaho. “I feel like this is what a real scientist does,” wrote one student in response to a survey question. And indeed, it is just what real scientists do.

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