Bioorthogonal Metabolic Labeling Experiments to Introduce Undergraduate Students to Interdisciplinarity at the Interface of Chemistry and Biology

Abstract

Chemists have always designed and deployed cross-disciplinary approaches that interface chemistry with other disciplines to proffer solutions to many human problems. We designed a laboratory experiment that implements chemistry concepts in a biological model to prime undergraduate students to appreciate interdisciplinarity as an approach to solving complex problems in contemporary society. The experiments can also be implemented with graduate students transitioning to chemical biology research. The experiment introduces students to classical and emerging chemistry and molecular biology techniques─mammalian cell culture, bioorthogonal metabolic labeling, azide–alkyne cycloaddition reaction (“click” chemistry), microplate photometry, gel electrophoresis, and far-western blot analysis─that are routinely used in research at the interface of chemistry and biology. The students cultured a Chinese hamster ovary cell line (CHO-K1) and metabolically labeled the cellular sialoglycans with azide groups. Next, they used a click chemistry reaction to bioconjugate a fluorogenic molecule to the labeled sialoglycans, enabling the detection of the glycans using microplate photometry or far-western blot analysis. The experiment created a context for a first-hand demonstration of bioorthogonal chemical reaction, a concept novel to most undergraduates with traditional chemistry (organic, inorganic, physical chemistry, and analytical) background. The experience allows the students to apply and connect organic chemistry, bioanalytical chemistry, and molecular biology concepts while learning techniques such as microplate reading, SDS PAGE, and western blot imaging that are indispensable to the growing fields of drug discovery, chemical toxicology, chemical biology, and molecular biology. This experiment is ideal for preparing and motivating students to pursue future research opportunities at the interface of chemistry and biology.