Frontiers in Chemical Biology Seminar
Bryan Dickinson earned his B.S. in Biochemistry from the University of Maryland, College Park and his Ph.D. in Chemistry from the University of California at Berkeley for work performed with Professor Christopher Chang. His graduate work focused on the synthesis and application of small molecule fluorescent probes for the detection of hydrogen peroxide in living systems. Then, as a Jane Coffin Childs Memorial postdoctoral fellow with Professor David Liu at Harvard University, he developed new methods to rapidly evolve proteins to perform novel functions. Bryan joined the faculty at the University of Chicago in the Department of Chemistry in the Summer of 2014 and is a member of the University of Chicago Comprehensive Cancer Center. The Dickinson Group employs synthetic organic chemistry, molecular evolution, and protein design to develop molecular technologies to study chemistry in living systems. The group's current primary research interests include: 1) how lipid modifications on proteins are controlled and regulate cell signaling, 2) developing new evolution technologies to reprogram and control biomolecular interactions, and 3) engineering protein-based systems to understand and exploit epitranscriptomic regulation. The motivating principle of the Dickinson Group is that our ability as chemists to create functional molecules through both rational and evolutionary approaches will lead to new breakthroughs in biology and biotechnology.
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.