The ability to modify macromolecules in a controlled manner to probe function is a key aspect of chemical biology. Despite the increasing applicability and significant research advances being made with chemical biology tools to manipulate biomolecules, little time is spent in traditional lectures and laboratory courses on the ability to robustly engineer proteins with these new technologies. The development of chemical biology laboratory courses is limited due to time and resources required to develop a new course. Furthermore, meaningful undergraduate research experiences are key for education and development, but mentor capacity and laboratory space for undergraduate research is at a premium. For these reasons, we have developed, implemented, and scaled an independent, research-based laboratory course in which students use genetic code expansion to modify proteins in a controlled and directed manner and explore the utility of altering biomolecules with chemical biology tools. Here, we present the course design and content in which students use genetic code expansion to assess the effects of incorporation of non-canonical amino acids on protein characteristics using model proteins thermostable human carbonic anhydrase II, E. coli HPII catalase, and Drosophila dynein light-chain LC8. The flexibility and versatility of genetic code expansion affords it a unique advantage for a biochemistry or chemical biology course platform. By providing an array of non-canonical amino acids and residues to substitute, students are provided with 21 unique options for each protein, making the execution of many independent studies feasible. Beyond the use of genetic code expansion, this course highlights hypothesis and experiment development, understanding of the central dogma, execution and comprehension of basic laboratory skills, critical thinking, and use of primary literature and culminates in writing a scientific manuscript. This course can be scaled for class size and time frame and tuned to the available resources, interests, and skills of students and instructors and has been successfully implemented at both a large, research university and a small, primarily undergraduate institution.

Unnatural chemical biology: Implementable, scalable, and tunable chemical biology undergraduate lab course

2019 Fall National Meeting

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