2017.06.21 Unleashing the power of biology - A synthetic biology approach
题 目： Unleashing the power of biology- A synthetic biology approach
报告人：Dr. Shuyi Zhang
Department of Bioengineering，Massachusetts Institute of Technology
时 间： 2017-06-21 (周三), 14:00-15:00
主持人： 汤超 教授
摘 要:Understanding and harnessing the capability to build genetic circuits and control gene expression levels under different growth conditions will offer potential solutions to both biotechnological and biomedical challenges. Previous genetic circuits have been built using transcription factor logic gates. However, the small number of existing orthogonal gates limits the size of circuits that can be built. CRISPR/dCas9 gates, which employ small guide RNAs (sgRNAs) to repress cognate promoters, offer a potential solution to this issue due to the ease by which orthogonal sgRNA:promoter pairs can be designed. However, the non-cooperative response curve of the sgRNA gate causes the transcriptional signal to decay at each layer, thereby limiting the depth of circuits that can be built. In this study, the PAM recognition region of dCas9 was mutated and a DNA binding protein (PhlF) was fused to this dCas9 variant for targeted repression. The fused dCas9-PhlF complex had reduced toxicity and generated a more non-linear response curve. The reduced toxicity of the CRISPR/Cas gate as well as the conversion of response curve from an analog to digital shape will allow both computing paradigms to be pursued for building large and highly-scalable genetic circuits.
Shuyi Zhang received his B.S. degree in Biotechnology from Tsinghua University and obtained his Ph.D. degree in Microbiology from The Pennsylvania State University. He is currently a post-doctoral scholar in the Department of Bioengineering at Massachusetts Institute of Technology. His research focused on microbial physiology, metabolic engineering, and synthetic biology. He has published 11 research papers in Science, Energy and Environmental Science, Metabolic Engineering and other high quality journals. He has received many awards including the Fred Wedler outstanding dissertation award and the Chinese government award for outstanding self-financed students abroad.