Frontiers in Chemical Biology Seminar
Epitranscriptomic regulation controls information flow through the central dogma and provides unique opportunities for manipulating cell state at the RNA level. However, potential translational opportunities are impeded by a lack of understanding of the underlying mechanisms that guide RNA regulation and a lack of effective methods to target and control those processes. To address these challenges, I will present several new technologies developed by my group to better understand and control RNA regulatory systems. For example, we have developed a new evolution system to create reverse transcriptases that encode the sites and abundances of key RNA chemical modifications in mutational signatures for quantitative analysis of the locations and stoichiometries of the modifications by sequencing. We developed the CRISPR/Cas-inspired RNA targeting system (CIRTS), a new protein engineering strategy for constructing programmable RNA regulatory systems constructed entirely from human protein parts. The small size and human-derived nature of CIRTS provides a less-perturbative method for fundamental studies as well as a potential strategy to avoid immune issues when applied to epitranscriptomic therapies. Altogether, our work is motivated by technology creation around RNA biology to better fundamental regulation and develop new treatments for disease.