CAREER: Deciphering temporal events in mammalian cells using synthetic biology

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1553356Wong, Wilson A fundamental goal in biology is to understand how cells make decisions when faced with external signal. The proposed work will seek to understand how a cell, through genetic programs found in its genome, can distinguish signals that are varying in time (dynamics) and generate different outcomes. A 'learning by building' approach will be used to engineer genetic systems that can decode dynamic signals. Specifically, the PI will engineer novel genetic programs in living mammalian cells to enable it to interpret signal duration and sequence. This approach will also provide a unique opportunity to bridge basic and applied science, where the novel genetic systems may be used in commercial applications. A broader goal of this proposed work is to inspire students to design living cells, and train the next generation of workforce skilled in genetic engineering to address challenges in health, food, energy, and environment. The education and outreach plans of this proposed work will accomplish these objectives by providing direct and stimulating research experience for undergraduates and underprivileged high school students, and developing classroom and laboratory based courses for students, high school teachers, and researchers.This CAREER proposal aims to understand how genetic networks process information. Such understanding will provide insight into a wide range of cellular processes. The proposed work will seek to delineate the governing rules of genetic circuits that decipher dynamic signals and produce divergent output states with limited inputs. In particular, two dynamical features, cumulative signal duration and temporal-order will be studied. A forward engineering approach will be used to explore genetic circuits that can decode dynamics. Specifically, the PI will (i) develop DNA recombinase-based cascade circuits to decode signal duration, and (ii) engineer and characterize two-input recombinase-based temporal-order sensing circuits. A broader goal of this proposed work is to inspire students to design living cells, and train the next generation of workforce skilled in synthetic biology to address challenges in health, food, energy, and environment. The education and outreach plans will accomplish these objectives by providing mentored laboratory-based research experience for undergraduates and underprivileged high school students, and by developing classroom and laboratory based courses for students, high school teachers, and researchers.This CAREER award by the Biotechnology and Biochemical Engineering Program of the CBET Division is co-funded by the Systems and Synthetic Biology Program of the Division of Molecular and Cellular Biosciences.