报告人: Dr. Xin Zhou

 Department of Pharmaceutical Chemistry, University of California, San Francisco 

时间：2018年09月26日 下午3:00-4:30

地点：北京大学化学学院A区717报告厅.

欢迎各位老师同学参加！

Abstract:Cells function through well-controlled protein-protein interactions (PPIs). The ability to manipulate and engineer novel PPIs will lead to powerful tools to study and control cell signaling pathways. In the first example, we discovered a novel synthetic light-controlled protein-protein interaction, then developed a genetically encoded approach to control activities of several classes of proteins. We showed that the engineered photoswitchable kinases (psKinases) can spatiotemporally, reversibly, repeatedly and quantitatively control signaling activation. Using psMEK1, we established an all-optical cell-based assay for screening inhibitors specifically targeting MEK and ERK. Using the ability to activate Raf1 in short time windows, we uncovered a previously unknown direct and rapid inhibitory feedback loop from ERK to MEK1. Lastly, we demonstrated the ability of psMEK1, psRaf1 and psCDK5 to mediate light-induced developmental changes and synaptic vesicle transport in vivo. In the second example, we engineered a calcium-gated antibody-antigen interaction by phage display. These conformational selective antibodies modulate the activity of a target protein via distinct mechanisms. The activating antibodies facilitate protein dimerization, while the inhibitory antibodies drive protein monomerization or block protein active site. We are prepared to use these antibodies in a mouse disease model to determine (1) how the active form of the protein distributes in vivo, (2) how activation of the protein contributes to disease, and (3) whether inhibiting of this protein outside of a cell could prevent the disease. The engineering of these gated PPIs allowed us to make tools and therapeutics to investigate and control misregulated cellular mechanisms in diseases.

INTRODUCTION:

Dr. Xin Zhou

Department of Pharmaceutical Chemistry, University of California, San Francisco 

Dr. Xin Zhou holds a BS in Chemistry from Peking University in 2011. She received her Ph.D. in Bioengineering from Stanford University in 2017. Xin is now a Postdoctoral Fellow at University of California, San Francisco (UCSF). In her Ph.D., Xin identified, characterized, and optimized the first synthetic light-dependent protein-protein interaction, and designed a modular protein architecture to construct single-chain photoswitchable proteins, which include guanine nucleotide exchange factors and proteases (Science, 2012), kinases (Science, 2017), and Cas9s (ACS Chem Biol, 2018). Using these light-responsive proteins, Xin explored unknown cell signaling mechanisms and developed an all-optical drug screening platform. In her postdoc, Xin is a recipient of the prestigious Damon Runyon Cancer Research Foundation fellowship. She now works on developing novel antibody-based tools and immunotherapies to study and treat cancer and autoimmune disorders.