The yeast two-hybrid method as a learning vehicle for undergraduate independent research

While numerous materials focus on the formal training of biology undergraduate students in laboratory courses, such as in course-based undergraduate research experiences (CUREs), relatively few protocols are available to guide principal investigators and research mentors in one-on-one training of undergraduate student scientists in independent apprentice-style research projects in academic laboratory settings. This often leaves research mentors with the responsibility of developing and implementing curricula, resulting in considerable time investment and potentially unfavorable training outcomes. Here, we have developed an easy-to-follow manual to train undergraduate students who have some course-based knowledge but minimal research experience on the use of the yeast two-hybrid (Y2H) method of assessing protein-protein interactions. As a learning vehicle, the Y2H method teaches students many basic microbiology and molecular biology skills that are relevant to almost any molecular biology experiment. The Y2H method provides a visual readout (yeast growth) that is intuitive and easy to interpret, making it of special appeal to undergraduate researchers. In our experience using this manual to instruct undergraduate researchers, we have successfully and repeatedly trained undergraduate students with varying initial proficiencies and research sophistication in the Y2H technique. Moreover, we have found that this protocol improves understanding of multiple underlying complex biological concepts, as assessed through student answers to the evaluation questions we provide, and their formal end-of-semester written and oral reports.