Topology-dependent interference of synthetic gene circuit function by growth feedback.
Journal
Nature chemical biology
ISSN: 1552-4469
Titre abrégé: Nat Chem Biol
Pays: United States
ID NLM: 101231976
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
27
08
2019
accepted:
28
02
2020
pubmed:
7
4
2020
medline:
20
9
2020
entrez:
7
4
2020
Statut:
ppublish
Résumé
Growth-mediated feedback between synthetic gene circuits and host organisms leads to diverse emerged behaviors, including growth bistability and enhanced ultrasensitivity. However, the range of possible impacts of growth feedback on gene circuits remains underexplored. Here we mathematically and experimentally demonstrated that growth feedback affects the functions of memory circuits in a network topology-dependent way. Specifically, the memory of the self-activation switch is quickly lost due to the growth-mediated dilution of the circuit products. Decoupling of growth feedback reveals its memory, manifested by its hysteresis property across a broad range of inducer concentration. On the contrary, the toggle switch is more refractory to growth-mediated dilution and can retrieve its memory after the fast-growth phase. The underlying principle lies in the different dependence of active and repressive regulations in these circuits on the growth-mediated dilution. Our results unveil the topology-dependent mechanism on how growth-mediated feedback influences the behaviors of gene circuits.
Identifiants
pubmed: 32251409
doi: 10.1038/s41589-020-0509-x
pii: 10.1038/s41589-020-0509-x
pmc: PMC7246135
mid: NIHMS1569849
doi:
Substances chimiques
Escherichia coli Proteins
0
Green Fluorescent Proteins
147336-22-9
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
695-701Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM106081
Pays : United States
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