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Engineering a Model Cell for Rational Tuning of GPCR Signaling.

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Shaw, William M 
Yamauchi, Hitoshi 
Mead, Jack 
Gowers, Glen-Oliver F 
Bell, David J 

Abstract

G protein-coupled receptor (GPCR) signaling is the primary method eukaryotes use to respond to specific cues in their environment. However, the relationship between stimulus and response for each GPCR is difficult to predict due to diversity in natural signal transduction architecture and expression. Using genome engineering in yeast, we constructed an insulated, modular GPCR signal transduction system to study how the response to stimuli can be predictably tuned using synthetic tools. We delineated the contributions of a minimal set of key components via computational and experimental refactoring, identifying simple design principles for rationally tuning the dose response. Using five different GPCRs, we demonstrate how this enables cells and consortia to be engineered to respond to desired concentrations of peptides, metabolites, and hormones relevant to human health. This work enables rational tuning of cell sensing while providing a framework to guide reprogramming of GPCR-based signaling in other systems.

Description

Keywords

G protein-coupled receptor, Saccharomyces cerevisiae, biosensor, cell signaling, cell-to-cell communication, genome engineering, synthetic biology, Gene Expression, Genetic Engineering, Humans, Pheromones, Receptors, G-Protein-Coupled, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Signal Transduction, Transcription Factors

Journal Title

Cell

Conference Name

Journal ISSN

0092-8674
1097-4172

Volume Title

177

Publisher

Elsevier BV
Sponsorship
Biotechnology and Biological Sciences Research Council (BB/M00015X/2)
BBSRC