Synthetic Genetic Systems for Continuous Evolution and Barcoding in vivo
Seminar | December 5 | 12-1 p.m. | 106 Stanley Hall
Chang C. Liu, University of California, Irvine
We are interested in building genetic systems that have extremely high mutation rates in order to speed up the evolution of target proteins and enzymes in vivo as well as to record transient information, such as lineage relationships or exposure to biological stimuli, as genetic information in situ. I will present work on two genetic systems that we have recently developed. First, I will describe a highly error-prone yeast orthogonal DNA replication (OrthoRep) system that mutates user-selected genes at a base pair substitution (bps) rate of 1e-5 without any increase in the genomic mutation rate (1e-10 bps). This ~100,000-fold mutational acceleration allows for the rapid continuous evolution of target biomolecules entirely in vivo using a simple serial passaging process amenable to extensive repetition. I will discuss the application of OrthoRep in understanding drug resistance and evolving useful enzymes and proteins. Second, I will describe work on the construction of a rapidly mutating locus in mammalian cells called CHYRON (Cell HistorY Recording by Ordered iNsertion), where our ultimate goal is to achieve single-cell resolution lineage tracing in developing animals.