Evidence map›Paper›PMID 34739875›Full record

ArticleCell systems2022

A synthetic gene circuit for imaging-free detection of signaling pulses.

Pavithran T Ravindran, Sarah McFann, Richard H Thornton, Jared E Toettcher

Abstract read
In one paragraph

Article in Cell systems, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing 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

13 citing papers in PubMed.

  1. Article
  2. Article
  3. Enzymatic DNA Reaction Networks for Orchestrating Stimuli-Dependent Temporal Molecular Pulse.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors.

Pavithran T RavindranDepartment of Molecular Biology, Princeton University, Princeton, NJ 08544, USA; Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA.
Sarah McFannDepartment of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA; Lewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.
Richard H ThorntonDepartment of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Jared E ToettcherDepartment of Molecular Biology, Princeton University, Princeton, NJ 08544, USA. Electronic address: toettcher@princeton.edu.

Funding

PREDOCTORAL TRAINING PROGRAM IN GENETICST32GM007388 · NIGMS · PRINCETON UNIVERSITY · PI CRISTEA, ILEANA M. · 1985 to 2022
$27.4M
Harnessing optogenetics to diagnose and therapeutically rewire cancer cell signalingDP2EB024247 · NIBIB · PRINCETON UNIVERSITY · PI TOETTCHER, JARED E · 2016 to 2016
$2.4M
NIBIB NIH HHS DP2 EB024247NIGMS NIH HHS T32 GM007388
6 · The paper itself

Abstract

Cells employ intracellular signaling pathways to sense and respond to changes in their external environment. In recent years, live-cell biosensors have revealed complex pulsatile dynamics in many pathways, but studies of these signaling dynamics are limited by the necessity of live-cell imaging at high spatiotemporal resolution. Here, we describe an approach to infer pulsatile signaling dynamics from a single measurement in fixed cells using a pulse-detecting gene circuit. We computationally screened for circuits with the capability to selectively detect signaling pulses, revealing an incoherent feedforward topology that robustly performs this computation. We implemented the motif experimentally for the Erk signaling pathway using a single engineered transcription factor and fluorescent protein reporter. Our "recorder of Erk activity dynamics" (READer) responds sensitively to spontaneous and stimulus-driven Erk pulses. READer circuits open the door to permanently labeling transient, dynamic cell populations to elucidate the mechanistic underpinnings and biological consequences of signaling dynamics.

Indexed as

Gene Regulatory NetworksGenes, SyntheticGene Expression RegulationMAP Kinase Signaling SystemSignal Transductioncell signalingnetwork motifssignaling dynamicssynthetic biology

Identifiers

PMID34739875
PMCPMC8857027

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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.