Evidence map›Paper›PMID 31578371›Full record

ArticleNature communications2019

A tunable dual-input system for on-demand dynamic gene expression regulation.

Elisa Pedone, Lorena Postiglione, Francesco Aulicino, Dan L Rocca, Sandra Montes-Olivas, Mahmoud Khazim, Diego di Bernardo, Maria Pia Cosma, Lucia Marucci

Abstract read
In one paragraph

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing 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

23 citing papers in PubMed.

  1. Article
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  5. Article
  6. Efficient gene delivery admitted by small metabolites specifically targeting astrocytes in the mouse brain.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. The context matrix: Navigating biological complexity for advanced biodesign.Frontiers in bioengineering and biotechnology · 2022
    Article
  17. Pulsed Electric Fields Alter Expression of NF-κB Promoter-Controlled Gene.International journal of molecular sciences · 2021
    Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Elisa PedoneDepartment of Engineering Mathematics, University of Bristol, Bristol, BS8 1UB, UK. elisa.pedone@bristol.ac.uk.
Lorena PostiglioneDepartment of Engineering Mathematics, University of Bristol, Bristol, BS8 1UB, UK.
Francesco AulicinoBrisSynBio, Bristol, BS8 1TQ, UK.
Dan L RoccaDepartment of Engineering Mathematics, University of Bristol, Bristol, BS8 1UB, UK. dan.rocca@bristol.ac.uk.
Sandra Montes-OlivasDepartment of Engineering Mathematics, University of Bristol, Bristol, BS8 1UB, UK.
Mahmoud KhazimDepartment of Engineering Mathematics, University of Bristol, Bristol, BS8 1UB, UK.
Diego di BernardoTelethon Institute of Genetics and Medicine Via Campi Flegrei 34, 80078, Pozzuoli, Italy.ORCID http://orcid.org/0000-0002-1911-7407
Maria Pia CosmaCentre for Genomic Regulation (CRG), Dr Aiguader 88, 08002, Barcelona, Spain.
Lucia MarucciDepartment of Engineering Mathematics, University of Bristol, Bristol, BS8 1UB, UK. lucia.marucci@bristol.ac.uk.

Funding

Biotechnology and Biological Sciences Research Council BB/L01386X/1Medical Research Council MR/N021444/1
6 · The paper itself

Abstract

Cellular systems have evolved numerous mechanisms to adapt to environmental stimuli, underpinned by dynamic patterns of gene expression. In addition to gene transcription regulation, modulation of protein levels, dynamics and localization are essential checkpoints governing cell functions. The introduction of inducible promoters has allowed gene expression control using orthogonal molecules, facilitating its rapid and reversible manipulation to study gene function. However, differing protein stabilities hinder the generation of protein temporal profiles seen in vivo. Here, we improve the Tet-On system integrating conditional destabilising elements at the post-translational level and permitting simultaneous control of gene expression and protein stability. We show, in mammalian cells, that adding protein stability control allows faster response times, fully tunable and enhanced dynamic range, and improved in silico feedback control of gene expression. Finally, we highlight the effectiveness of our dual-input system to modulate levels of signalling pathway components in mouse Embryonic Stem Cells.

Indexed as

AnimalsAnti-Infective AgentsCulture Media, ConditionedDoxycyclineFlow CytometryGene Expression RegulationHEK293 CellsHeLa CellsHumansLuminescent ProteinsMiceMicroscopy, ConfocalMouse Embryonic Stem CellsRed Fluorescent ProteinTrimethoprimAnti-Infective AgentsCulture Media, ConditionedDoxycyclineLuminescent ProteinsRed Fluorescent ProteinTrimethoprim

Identifiers

PMID31578371
PMCPMC6775159

What Socratic 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 Socratic graph.