title: Synthetic Biology Platform for Sensing and Integrating Endogenous Transcriptional Inputs in Mammalian Cells.
abstract: One of the goals of synthetic biology is to develop programmable artificial gene networks that can transduce multiple endogenous molecular cues to precisely control cell behavior. Realizing this vision requires interfacing natural molecular inputs with synthetic components that generate functional molecular outputs. Interfacing synthetic circuits with endogenous mammalian transcription factors has been particularly difficult. Here, we describe a systematic approach that enables integration and transduction of multiple mammalian transcription factor inputs by a synthetic network. The approach is facilitated by a proportional amplifier sensor based on synergistic positive autoregulation. The circuits efficiently transduce endogenous transcription factor levels into RNAi, transcriptional transactivation, and site-specific recombination. They also enable AND logic between pairs of arbitrary transcription factors. The results establish a framework for developing synthetic gene networks that interface with cellular processes through transcriptional regulators.
authors.affiliation: Department of Biosystems Science and Engineering, Swiss Federal Institute of Technology (ETH Zurich), Mattenstrasse 26, 4058 Basel, Switzerland.
authors.forename: Bartolomeo
authors.initials: B
authors.lastname: Angelici
authors.affiliation: Department of Biosystems Science and Engineering, Swiss Federal Institute of Technology (ETH Zurich), Mattenstrasse 26, 4058 Basel, Switzerland.
authors.forename: Erik
authors.initials: E
authors.lastname: Mailand
authors.affiliation: Department of Biosystems Science and Engineering, Swiss Federal Institute of Technology (ETH Zurich), Mattenstrasse 26, 4058 Basel, Switzerland.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Haefliger
authors.affiliation: Department of Biosystems Science and Engineering, Swiss Federal Institute of Technology (ETH Zurich), Mattenstrasse 26, 4058 Basel, Switzerland. Electronic address: kobi.benenson@bsse.ethz.ch.
authors.forename: Yaakov
authors.initials: Y
authors.lastname: Benenson
mesh_terms: D000818:Animals; D015374:Biosensing Techniques; D045744:Cell Line, Tumor; D053263:Gene Regulatory Networks; D045325:HCT116 Cells; D057809:HEK293 Cells; D006367:HeLa Cells; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D006801:Humans; D060847:Metabolic Engineering / Q000379:methods*; D034622:RNA Interference; D011995:Recombination, Genetic; D015398:Signal Transduction; D058615:Synthetic Biology / Q000379:methods*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D014157:Transcription Factors