Phage display is a widely used tool for the directed evolution of peptide ligands with novel properties. My research has utilized genetic code expansion to encode ncAAs into phage-displayed peptide libraries, thereby greatly expanding their chemical diversity. We have used this technology to identify potent inhibitors of promising anticancer drug targets. Currently, I am using phage-assisted non-continuous evolution to evolve aminoacyl-tRNA synthetases and tRNAs for genetic code expansion.
GENETIC CODE REPROGRAMMING
The standard genetic code is composed of 64 3-base codons that, in most organisms, encode 20 different amino acids. Traditio-nally, non-natural amino acids (ncAAs) are installed into proteins in res-ponse to redefined nonsense (stop) codons. Since there are only three nonsense codons, the number of unique ncAAs that can be installed into proteins is limited to three. I am working to reprogram the genetic code by redefining sense codons to expand the number of ncAAs that can be encoded.
Proteins are genetically encoded polymers composed of amino acids. The Center for Genetically Encoded Materials (C-GEM) is a highly collaborative, interdisciplinary research team with the goal of repurposing the E. coli translational machinery to generate sequence-defined polymers composed of monomers that are not alpha-amino acids. As a part of this team I am using my expertise in aminoacyl-tRNA synthetase evolution to engineer enzymes that aminoacylate tRNA with building blocks for aramids, polyolefins, polyurethanes, and other important materials.