We have discovered that cells uniquely reprogram the abundances of tRNAs and their chemical modifications (tRNA pools) in response to diverse cellular stresses, including those associated with the production of foreign recombinant proteins. These changes in the tRNA pool bias the translation of the stress response proteins necessary for survival and maintenance of productivity by enhancing translation of their codon-biased mRNAs.

These stress-induced changes to the cell’s tRNA pool cannot be predicted and must be measured using a suite of omics technologies, as each stressor elicits a unique translational reprogramming profile. Our mass spectrometry-based omics approaches measure changes in the cell’s proteome and epitranscriptome in response to protein production and are supported by >50 publications.

Our proprietary epitranscriptome-centric software platform integrates the collected omics data and leverages novel epitranscriptomics-centric algorithms to identify the translational drivers of the cell’s stress response to enhance protein productivity. The cell line is then translationally engineered at the proteomic and epitranscriptomic levels to enhance production and maintain biofidelity of the target recombinant protein.