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Engineering a model cell for rational tuning of GPCR signaling

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Title: Engineering a model cell for rational tuning of GPCR signaling
Authors: Shaw, W
Yamauchi, H
Mead, J
Gowers, G
Bell, D
Oling, D
Larsson, N
Wigglesworth, M
Ladds, G
Ellis, T
Item Type: Journal Article
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.
Issue Date: 18-Apr-2019
Date of Acceptance: 13-Feb-2019
URI: http://hdl.handle.net/10044/1/67615
DOI: 10.1016/j.cell.2019.02.023
ISSN: 0092-8674
Publisher: Elsevier (Cell Press)
Start Page: 782
End Page: 796.e27
Journal / Book Title: Cell
Volume: 177
Issue: 3
Copyright Statement: © 2019 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
Keywords: Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Cell Biology
PROTEIN-COUPLED-RECEPTOR
PHEROMONE RESPONSE PATHWAY
BETA-GAMMA COMPLEX
SACCHAROMYCES-CEREVISIAE
FUNCTIONAL EXPRESSION
GENE-EXPRESSION
KINASE CASCADE
MATING PATHWAY
ALPHA-SUBUNIT
YEAST
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
Humans
Saccharomyces cerevisiae
Saccharomyces cerevisiae Proteins
Receptors, G-Protein-Coupled
Transcription Factors
Pheromones
Genetic Engineering
Signal Transduction
Gene Expression
Developmental Biology
06 Biological Sciences
11 Medical and Health Sciences
Publication Status: Published
Online Publication Date: 2019-04-04
Appears in Collections:Bioengineering
Department of Infectious Diseases
Faculty of Medicine
Faculty of Engineering