Title: Synthetic Genetics Systems for Rapid Mutation and Continuous Evolution in Vivo
Abstract: 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 durable genetic information in situ. I will primarily discuss our work on building OrthoRep, a highly error-prone orthogonal DNA replication system that mutates user-selected genes at a rate of 1e-5 substitutions per base (s.p.b.) without any increase in the genomic mutation rate (1e-10 s.p.b). 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 exploring drug resistance, studying protein evolution, and evolving useful enzymes and proteins. I will also comment on the value of scalable continuous evolution in searching for and understanding old and new biomolecular function going forward.
Bio: Chang Liu is an Assistant Professor of Biomedical Engineering, Chemistry, and Molecular Biology and Biochemistry at UC Irvine. Starting at a young age, Liu pursued a career as a concert pianist, but shifted his primary interest to chemistry when he was a sophomore at Harvard, where he conducted undergraduate research with Professor Stuart Schreiber. After graduating summa cum laude and Phi Beta Kappa with a degree in chemistry, Liu joined the laboratory of Professor Peter Schultz at the Scripps Research Institute as a Hertz Fellow and an NSF Fellow. At Scripps, Liu expanded the genetic code of bacteria for the co-translational incorporation of otherwise post-translational modifications and provided the first demonstrations that expanded genetic codes can be selectively advantageous in the evolution of novel protein function. After earning his PhD in chemistry, Liu became a Miller Fellow at UC Berkeley. Working with Professor Adam Arkin, Liu conducted research in the field of synthetic biology and developed methods for the predictable creation of complex regulatory systems. In 2013, Liu started his lab at UC Irvine.
Professor Liu’s research is in the fields of synthetic biology, chemical biology, and directed evolution. He is particularly interested in engineering specialized genetic systems for rapid mutation and evolution in vivo to address problems ranging from protein engineering to developmental biology. For his group’s work, Professor Liu has been recognized with a number of awards including the Sloan Research Fellowship, the NIH New Innovator Award, the Beckman Young Investigator Award, the Dupont Young Professor Award, the ACS Synthetic Biology Young Innovator Award, the Vaughan Lectureship at Caltech, and the Moore Inventor Fellowship.