Evidence map›Paper›PMID 27111147›Full record

ArticleACS synthetic biology2016

Efflux Pump Control Alters Synthetic Gene Circuit Function.

Junchen Diao, Daniel A Charlebois, Dmitry Nevozhay, Zoltán Bódi, Csaba Pál, Gábor Balázsi

Abstract read
In one paragraph

Article in ACS synthetic biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing 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

9 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Multiscale effects of heating and cooling on genes and gene networks.Proceedings of the National Academy of Sciences of the United States of America · 2018
    Article
  9. Negative Regulation Gene Circuits for Efflux Pump Control.Methods in molecular biology (Clifton, N.J.) · 2018
    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

6 authors.

Junchen DiaoDepartment of Systems Biology, The University of Texas MD Anderson Cancer Center , Unit 950, 7435 Fannin Street, Houston, Texas 77054, United States.
Daniel A CharleboisThe Louis and Beatrice Laufer Center for Physical & Quantitative Biology, Stony Brook University , 115C Laufer Center, Z-5252, Stony Brook, New York 11794, United States.
Dmitry NevozhayDepartment of Systems Biology, The University of Texas MD Anderson Cancer Center , Unit 950, 7435 Fannin Street, Houston, Texas 77054, United States.
Zoltán BódiInstitute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences , Temesvári krt. 62., H-6726 Szeged, Hungary.
Csaba PálInstitute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences , Temesvári krt. 62., H-6726 Szeged, Hungary.
Gábor BalázsiDepartment of Systems Biology, The University of Texas MD Anderson Cancer Center , Unit 950, 7435 Fannin Street, Houston, Texas 77054, United States.

Funding

Connecting the selection of noisy gene expression deviants to genetic evolutionDP2OD006481 · OD · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI BALAZSI, GABOR · 2009 to 2009
$2.3M
European Research Council 202591NIH HHS DP2 OD006481
6 · The paper itself

Abstract

Synthetic biology aims to design new biological systems for predefined purposes, such as the controlled secretion of biofuels, pharmaceuticals, or other chemicals. Synthetic gene circuits regulating an efflux pump from the ATP-binding cassette (ABC) protein family could achieve this. However, ABC efflux pumps can also drive out intracellular inducer molecules that control the gene circuits. This will introduce an implicit feedback that could alter gene circuit function in ways that are poorly understood. Here, we used two synthetic gene circuits inducible by tetracycline family molecules to regulate the expression of a yeast ABC pump (Pdr5p) that pumps out the inducer. Pdr5p altered the dose-responses of the original gene circuits substantially in Saccharomyces cerevisiae. While one aspect of the change could be attributed to the efflux pumping function of Pdr5p, another aspect remained unexplained. Quantitative modeling indicated that reduced regulator gene expression in addition to efflux pump function could fully explain the altered dose-responses. These predictions were validated experimentally. Overall, we highlight how efflux pumps can alter gene circuit dynamics and demonstrate the utility of mathematical modeling in understanding synthetic gene circuit function in new circumstances.

Indexed as

Gene Regulatory NetworksGenes, SyntheticModels, TheoreticalATP-Binding Cassette TransportersDose-Response Relationship, DrugDoxycyclineGene Expression Regulation, FungalGreen Fluorescent ProteinsRecombinant ProteinsSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsTetracyclineATP-Binding Cassette TransportersDoxycyclineGreen Fluorescent ProteinsPDR5 protein, S cerevisiaeRecombinant ProteinsSaccharomyces cerevisiae ProteinsTetracyclineefflux pumpfeedbackstochastic simulationsynthetic gene circuit

Identifiers

PMID27111147
PMCPMC5752098

What OpenQuestion holds

Textmetadata
LicenceTDM
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.