报告题目：Molecular Engineering for Imaging and Reprogramming in Live Cells
报 告 人：Dr. Peter Yingxiao Wang, Professor of Bioengineering, Institute of Engineering in Medicine, USA
报告时间：7月24日，10：00 - 11：00
联 系 人：齐颖新， firstname.lastname@example.org
Signaling molecules and their activities are well coordinated in space and time to regulate cellular functions in response to mechanical and chemical microenvironment. Based on fluorescent resonance energy transfer (FRET), we have developed genetically encoded biosensors to monitor the dynamic molecular activities (such as Src and FAK activities) in live cells at subcellular compartments when cells interact with their neighbors or mechanical/chemical microenvironment. In a recent study, we show that a ubiquitous signaling protein, Src Homology 2 (SH2) Domain-containing Protein Tyrosine Phosphatase 2 (Shp2), displayed unexpected plasticity of conformational changes via intramolecular interactions within Shp2 (cis-interaction). We found that two phosphorylated regulatory tyrosines upon stimulated phosphorylation can compete for the cis-interaction of the same SH2 domain within Shp2 to achieve plasticity. The antagonistic combination of contextual amino acid sequence and position can create a relatively small difference between the two phosphorylated tyrosines in their overall competitiveness for intramolecular conformational regulation. Enlarging this difference by swapping the sequences at the two tyrosine positions resulted in loss of conformational plasticity and reprogrammed downstream ERK signaling dynamics. We have further engineered a machinery molecule based on Shp2 which allows an integrated capability of imaging and manipulation of single cell life. We suggest that this strategy can serve as a general and basic design principle for natural and synthetic proteins, with their conformations and functions tunable to regulate downstream physiological consequences. As such, molecular engineering and biosensor development can provide powerful tools for the imaging and manipulation of cellular lives at single cell levels.
Dr. Wang obtained his bachelor's and master's degrees in Mechanics and Fluid Mechanics from Peking University, Beijing, P.R. China, in 1992 and 1996, respectively. He received his Ph.D. degree in Bioengineering from the University of California, San Diego Jacobs School of Engineering in 2002 and continued his postdoctoral work at UC San Diego working under Bioengineering Professor Shu Chien and Professor Roger Y. Tsien in the Department of Pharmacology. Before joining the UC San Diego faculty in 2012, he was an associate professor at the University of Illinois, Urbana-Champaign (UIUC), Department of Bioengineering and a full-time faculty member in the Beckman Institute for Advanced Science and Technology at the University of Illinois. He was also affiliated with the Department of Molecular and Integrative Physiology, Neuroscience Program, the Center for Biophysics and Computational Biology, and Institute of Genomic Biology at UIUC. Dr. Wang is the recipient of the Wallace H. Coulter Early Career Award (both Phase I and Phase II), the National Science Foundation CAREER Award, and National Institutes of Health Independent Scientist Award. His research is supported by the National Institutes of Health, National Science Foundation, and private foundations. Dr. Wang teaches undergraduate and graduate courses on molecular engineering, live cell imaging, and mechanobiology.