On December 12th, 2017，Prof. Ralf Jauch from the Guangzhou Institutes of Biomedicine and Health, which is affiliated with the Chinese Academy of Sciences, was invited to give a one-hour presentation at the Life Science Seminar on our campus. His talk was entitled: “Enhancing Cellular Reprogramming by Directed Factor Evolution”. Prof. Jauch was met with an enthusiastic reception by a diverse audience, including researchers, professionals and students from other research institutions.
Prof. Jauch made a systematic description focusing on the sequence-function relationship of transcription factor (TF) mediated cell fate conversions. First, Prof. Jauch introduced the assays performed to analyze the formation of TF complexes on regulatory DNA, including structural modeling, quantitative biochemical assays and genomics techniques (RNAseq, ChIPseq). By contrasting the dynamic binding and gene regulation of paralogous TFs and engineered factors, Prof. Jauch discussed how “enhancer codes” are deciphered in cell fate reprogramming and in the identification of functionally critical structural elements. Subsequently, Prof. Jauch illustrated how combinations of lineage specifying TFs (including SOX, OCT, PAX and FOX family proteins) work together to guide cell face conversions in a step-wise manner. Prof. Jauch’s research team hypothesized that native TFs are not optimized to direct artificial cell fate conversions and that they could be artificially improved. He presented several case studies showing how protein engineering could switch and enhance TF-driven cell fate conversions. He proposed that this strategy presents a general paradigm that could be applied to any biomolecule-driven cell conversion system with utility in regenerative biomedicine.