A synthetic gene circuit for imaging-free detection of signaling pulses.
cell signaling
network motifs
signaling dynamics
synthetic biology
Journal
Cell systems
ISSN: 2405-4720
Titre abrégé: Cell Syst
Pays: United States
ID NLM: 101656080
Informations de publication
Date de publication:
16 02 2022
16 02 2022
Historique:
received:
17
02
2021
revised:
20
07
2021
accepted:
14
10
2021
pubmed:
6
11
2021
medline:
20
4
2022
entrez:
5
11
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34739875
pii: S2405-4712(21)00413-0
doi: 10.1016/j.cels.2021.10.002
pmc: PMC8857027
mid: NIHMS1756933
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
131-142.e13Subventions
Organisme : NIBIB NIH HHS
ID : DP2 EB024247
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007388
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2021. Published by Elsevier Inc.
Déclaration de conflit d'intérêts
Declaration of interests J.E.T. is a member of the advisory board of Cell Systems. The authors declare no competing interests.
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