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Spatiotemporal Control Cellular Functions by Environment Stimuli-induced proximity

Spatiotemporal Control Cellular Functions by Environment Sti...

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第十届全国化学生物学学术会议

作者： Zeng,Guihua Wei,Yongyi Xuan,Weimin Li,Huanqiu Liang,Fu-Sen Wang,Wei Department of Chemistry and chemical Biology University of New Mexico School of Pharmacy East China University of Science & Technology

Spatiotemporal control of sophisticated cell signaling and functions is of considerable significance and broad impact on biomedical sciences. Recent efforts have been dedicated to engineer predictable and tailored cellular functions in responding to detected stimuli by rewiring or creating synthetic signal transduction pathways.1,2 However, the former requires extensive knowledge of these systems and is limited to existing paths, while the latter often goes through random mutations and selections, thus requires significant efforts and may still not obtain functional products as desired. New methods that circumvent these limitations will significantly contribute to the advance of the exciting research fields with broad applications of cell signaling, functions and gene/cell therapies. Towards this end, we recently introduced a novel technology, termed Environment Stimuli-induced proximity（ESIP）,3,4 as a new strategy for cellular engineering. This technology is based on the chemically induced proximity（CIP） methods,5 which utilize artificially applied chemical inducers to control the proximity between two chosen cellular proteins and in turn control the downstream biological events resulted from the protein association. However, it is difficult for these established CIP systems to mediate the translation of endogenous cellular signals into tailored cellular functions with spatiotemporal precision. We propose to construct the new ESIP systems by modifying the CIP chemical inducers to become also sensors for cellular environmental cues, which link the downstream cellular processes to specific signal cues as natural cellular signal transduction, but with rewired specificity and designed outputs. The presentation will discuss the details of our studies.

关键词： small molecule probe synthetic biology chemical induced proximity

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