Orthogonal Replication for Rapid Evolution and Synthetic Biology
The Center for Theoretical Biological Physics PRESENTS Dr. Chang Liu Assistant Professor Departments of Biomedical Engineering, Chemistry, Molecular Biology and Biochemistry University of California, Irvine
Abstract: We recently developed an orthogonal DNA replication (OrthoRep) system in the yeast Saccharomyces cerevisiae. OrthoRep exploits an unusual selfish DNA element consisting of a DNA plasmid–DNA polymerase pair that stably replicates in the cytoplasm of yeast. The spatial and mechanistic isolation of OrthoRep from genomic replication may have fundamental significance for protein engineering and synthetic biology. For protein engineering, it offers a general platform for rapid continuous evolution where genes encoded on the OrthoRep system can be made to undergo accelerated mutation without increasing the genomic mutation rate. For synthetic biology, OrthoRep is a platform that should enable the bottom-up construction of synthetic genetic and replication systems in vivo. In this talk, I will describe our recent systematic efforts to engineer our orthogonal DNA polymerase responsible to reach a range of high mutation rates, as well as the utility of targeted rapid mutagenesis in general. I will also comment on the importance of building orthogonal central dogma components for protein engineering, directed evolution, and synthetic biology.
Bio: Chang Liu is an Assistant Professor of Biomedical Engineering, Chemistry, and Molecular Biology and Biochemistry at UC Irvine. Liu was born in Shanghai, China and grew up in Tucson, AZ. Liu graduated summa cum laude from Harvard with a bachelor’s degree in chemistry and received his PhD in Chemical Biology from the Scripps Research Institute. He carried out synthetic biology research as a Miller Fellow at UC Berkeley and started his lab at UC Irvine in 2013. 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 mutagenesis and evolution, and creating synthetic organisms that use new building blocks for their informational and functional macromolecules. These systems can then be widely applied for the engineering, discovery, and understanding of biological function. For his work, Prof. Liu has numerous awards, including the Sloan Research Fellowship, the NIH New Innovator Award, the Beckman Young Investigator Award, and the Dupont Young Professor Award.
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