Editing the yeast genome

It’s unusual for undergraduate students to publish academic papers as first authors, but Matthew Zackin, E22, was up to the task with the support of his faculty advisor, Bright Futures Assistant Professor James Van Deventer, and the research team at Tufts School of Engineering. Through the Nathan Gantcher Summer Scholars Program, juniors and seniors across all departments at Tufts can get involved in a 10-week research project. In the Department of Chemical and Biological Engineering, Zackin worked in the Van Deventer Laboratory on researching changes to the yeast genome that allow cells to add amino acids to their genetic code more efficiently.

The Van Deventer Laboratory pursues the engineering of more “drug-like” proteins and finding new ways to treat cancer and other complex diseases with biomolecular engineering, synthetic biology, and chemical biology. Zackin, PhD alum Jessica Stieglitz, EG21, and Bright Futures Assistant Professor James Van Deventer recently identified yeast gene knockouts that make it easier for yeast to add non-canonical amino acids (ncAAs) into proteins. NcAAs are amino acids that are not naturally part of the genetic code of a particular organism. Engineering cells for improved ncAA incorporation into proteins is a delicate balance – cells must change a portion of their genetic code, but still maintain the functions of the genome that enable cells to grow. The team screened thousands of yeast strains and found 55 candidate gene knockouts that may enhance ncAA incorporation in yeast. Detailed follow-up experiments on two of the most promising gene knockouts showed that these knockouts improved ncAA incorporation under diverse conditions. 

According to the authors, their paper, titled “Genome-wide screen for enhanced noncanonical amino acid incorporation in yeast,” is the first known study to screen gene knockouts across the entire genome of an organism with a specific focus on finding ways to enhance ncAA incorporation in proteins. Their research deepens the field’s understanding of genetic code expansion. “Adding a 21^st amino acid to the genetic code and getting a cell to treat this amino acid like any other amino acid is a grand challenge in synthetic biology. Solving this problem will open new applications in drug discovery, biomaterials, and basic biology,” says Van Deventer.

Over the course of the summer, Zackin gained hands-on lab experience while making key contributions to the growing field of genetic code manipulation. Zackin has recently started PhD studies in Biological Engineering at the Massachusetts Institute of Technology. His experience demonstrates the School of Engineering’s commitment to providing innovative undergraduate education with an emphasis on practical learning experiences.