Evidence map›Paper›PMID 32792645›Full record

ArticleCommunications biology2020

Engineering combinatorial and dynamic decoders using synthetic immediate-early genes.

Pavithran T Ravindran, Maxwell Z Wilson, Siddhartha G Jena, Jared E Toettcher

Abstract read
In one paragraph

Article in Communications biology, 2020. 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.

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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

4 authors.

Pavithran T RavindranDepartment of Chemical and Biological Engineering, Princeton University, Princeton, NJ, 08544, USA.
Maxwell Z WilsonDepartment of Molecular Biology, Princeton University, Princeton, NJ, 08544, USA.
Siddhartha G JenaDepartment of Molecular Biology, Princeton University, Princeton, NJ, 08544, USA.ORCID http://orcid.org/0000-0002-9750-0225
Jared E ToettcherDepartment of Molecular Biology, Princeton University, Princeton, NJ, 08544, USA. toettcher@princeton.edu.ORCID http://orcid.org/0000-0002-1546-4030

Funding

Harnessing optogenetics to diagnose and therapeutically rewire cancer cell signalingDP2EB024247 · NIBIB · PRINCETON UNIVERSITY · PI TOETTCHER, JARED E · 2016 to 2016
$2.4M
Cracking the signaling code: how ERK activity dynamics coordinate gene expression and differentiation in keratinocytesF31AR075398 · NIAMS · PRINCETON UNIVERSITY · PI JENA, SIDDHARTHA · 2019 to 2020
$91k
NIAMS NIH HHS F31 AR075398NIBIB NIH HHS DP2 EB024247NIH HHS DP2EB024247
6 · The paper itself

Abstract

Many cell- and tissue-level functions are coordinated by intracellular signaling pathways that trigger the expression of context-specific target genes. Yet the input-output relationships that link pathways to the genes they activate are incompletely understood. Mapping the pathway-decoding logic of natural target genes could also provide a basis for engineering novel signal-decoding circuits. Here we report the construction of synthetic immediate-early genes (SynIEGs), target genes of Erk signaling that implement complex, user-defined regulation and can be monitored by using live-cell biosensors to track their transcription and translation. We demonstrate the power of this approach by confirming Erk duration-sensing by FOS, elucidating how the BTG2 gene is differentially regulated by external stimuli, and designing a synthetic immediate-early gene that selectively responds to the combination of growth factor and DNA damage stimuli. SynIEGs pave the way toward engineering molecular circuits that decode signaling dynamics and combinations across a broad range of cellular contexts.

Indexed as

Genes, Immediate-EarlyGenes, SyntheticGenetic EngineeringAnimalsDNA DamageExtracellular Signal-Regulated MAP KinasesGene Expression RegulationKineticsMiceMitogensNIH 3T3 CellsProto-Oncogene Proteins c-fosSignal TransductionTranscription, GeneticExtracellular Signal-Regulated MAP KinasesMitogensProto-Oncogene Proteins c-fos

Identifiers

PMID32792645
PMCPMC7426417

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Registered trials

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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.