Rewiring the Central Dogma: Using Genetic Code Expansion to Teach Engineering Biology

Traditionally, the Central Dogma of molecular biology has been taught as a linear sequence of facts, emphasising recall of information flow from DNA to protein, rather than mechanistic understanding of the system. Further, many pedagogical approaches lack a prerogative of exploring beyond stipulated facts, thus neglecting the opportunity for students to apply this knowledge. Here, we present a synthetic biology–oriented approach to teaching the Central Dogma in a comprehensive, seven-day-long undergraduate course that integrates both lecture- and laboratory-based education. As a model example, we use genetic code expansion of green fluorescent protein (GFP), which, by repurposing a single codon, allows for site-specific incorporation of noncanonical amino acids (ncAAs). During theoretical teaching, we guide students through DNA transcription and RNA translation, tasking them with identification of specific steps whose engineering can enable ncAA incorporation. Moreover, we encourage our trainees to develop a flexible thinking mindset through the proposition of multiple mutable systems, challenging their perspectives through expansion of the genetic code in various contexts. In parallel, the practical sessions use standard molecular biology tools, available in most teaching laboratories to change the fluorescent properties of GFP through the use of ncAAs. Given the positive feedback from students, our approach demonstrates promise in promoting deeper mechanistic reasoning, preparing taught cohorts to engage with modern biological research.