Evidence map›Paper›PMID 30955892›Full record

ArticleCell2019

Engineering a Model Cell for Rational Tuning of GPCR Signaling.

William M Shaw, Hitoshi Yamauchi, Jack Mead, Glen-Oliver F Gowers, David J Bell, David Öling, Niklas Larsson, Mark Wigglesworth, Graham Ladds, Tom Ellis

Abstract read
In one paragraph

Article in Cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers.

0numbers the graph read from it
0cells of the map it votes in
106citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

106 citing papers in PubMed.

  1. Article
  2. Engineered Optogenetic Circuits In Yeast with Self-Sustained Outputs.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  3. Article
  4. Article
  5. Article
  6. Programming Next-Generation Synthetic Biosensors by Genetic Circuit Design.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  7. Article
  8. Mining Genetically Encoded Biosensors from Filamentous Fungi.Journal of fungi (Basel, Switzerland) · 2026
    Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. Probiotic-Based Materials as Living Therapeutics.Advanced materials (Deerfield Beach, Fla.) · 2026
    Review
  15. Article
  16. Article
  17. A yeast mating platform for multiplex screening of fungal GPCR-ligand interactions.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  18. Review
  19. Article
  20. Article

46 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

William M ShawDepartment of Bioengineering, Imperial College London, London SW7 2AZ, UK; Centre for Synthetic Biology, Imperial College London, London SW7 2AZ, UK.
Hitoshi YamauchiDepartment of Pharmacology, University of Cambridge, Cambridge CB2 1PD, UK.
Jack MeadDepartment of Pharmacology, University of Cambridge, Cambridge CB2 1PD, UK.
Glen-Oliver F GowersDepartment of Bioengineering, Imperial College London, London SW7 2AZ, UK; Centre for Synthetic Biology, Imperial College London, London SW7 2AZ, UK.
David J BellCentre for Synthetic Biology, Imperial College London, London SW7 2AZ, UK; SynbiCITE Innovation and Knowledge Centre, Imperial College London, London SW7 2AZ, UK.
David ÖlingDiscovery Biology, Discovery Sciences, Innovative Medicines and Early Development Biotech Unit, AstraZeneca R&D, 431 50 Mölndal, Sweden.
Niklas LarssonDiscovery Biology, Discovery Sciences, Innovative Medicines and Early Development Biotech Unit, AstraZeneca R&D, 431 50 Mölndal, Sweden.
Mark WigglesworthHit Discovery, Discovery Sciences, IMED Biotech Unit, AstraZeneca, Macclesfield SK10 4TG, UK. Electronic address: mark.wigglesworth@astrazeneca.com.
Graham LaddsDepartment of Pharmacology, University of Cambridge, Cambridge CB2 1PD, UK. Electronic address: grl30@cam.ac.uk.
Tom EllisDepartment of Bioengineering, Imperial College London, London SW7 2AZ, UK; Centre for Synthetic Biology, Imperial College London, London SW7 2AZ, UK. Electronic address: t.ellis@imperial.ac.uk.

Funding

Biotechnology and Biological Sciences Research Council BB/M00015X/2Biotechnology and Biological Sciences Research Council BB/M503381/1
6 · The paper itself

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.

Indexed as

Signal TransductionGene ExpressionGenetic EngineeringHumansPheromonesReceptors, G-Protein-CoupledSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsTranscription FactorsPheromonesReceptors, G-Protein-CoupledSaccharomyces cerevisiae ProteinsSTE12 protein, S cerevisiaeTranscription Factorsbiosensorcell signalingcell-to-cell communicationgenome engineeringG protein-coupled receptorSaccharomyces cerevisiaesynthetic biology

Identifiers

PMID30955892
PMCPMC6476273

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.