Reinterpreting the Genetic Code: Non-Canonical Amino Acids as Probes of Protein Synthesis in Complex Biological Systems

The genetic code, elucidated in the 1960s through the work of Nirenberg, Ochoa, and Khorana, provides a set of molecular instructions for turning DNA into proteins. What if we could change the meaning of those instructions and decide for ourselves how to interpret the genetic code? Over the last decade, cells have been outfitted with modified molecular machinery that enables them to use “non-canonical” amino acids to make proteins. These developments are leading to new approaches to macromolecular design, protein evolution, biological imaging, and proteome-wide analysis of cellular processes. This lecture will emphasize the use of non-canonical amino acids to analyze protein synthesis in time-resolved and cell-selective fashion in complex biological systems including live animals.