Research Summary
Biological engineers routinely harness the predictability of the central dogma to modify living organisms. This rule cannot be generally extended to manipulations of the central dogma itself, as even minor perturbations can have significant and often deleterious consequences on cellular viability. One such case is the ribosome, a colossal multi-component protein factory that functions as the nexus for cellular information and signaling events, integrating nutrient availability with growth dynamics and resource allocation.
Our lab is developing and applying methodologies to study the translation machinery of the cell using engineered orthogonal transcription-translation networks, overcoming challenges associated with ribosomal manipulation in vivo and providing a framework for high-throughput ribosomal interrogation. Our current work is focused on the (1) dissection of putative processivity-fidelity relationships during translation, (2) experimental validation of ribosomal divergence across prokaryotes, (3) prediction of ribosome-small molecule interactions and putative antibiotic resistance mechanisms, and (4) evaluating potential routes for evolution of the modern ribosome.