Multistable and dynamic CRISPRi-based synthetic circuits

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License: CC BY-NC 4.0
Secondary document(s)
Download: s41467-020-16574-1.pdf (1423.09 [Ko])
State: Public
Version: Final published version
License: Not specified
Serval ID
serval:BIB_9C270BA8A587
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Multistable and dynamic CRISPRi-based synthetic circuits
Journal
Nature communications
Author(s)
Santos-Moreno Javier, Tasiudi Eve, Stelling Joerg, Schaerli Yolanda
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Publication state
Published
Issued date
02/06/2020
Peer-reviewed
Oui
Volume
11
Number
1
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Gene expression control based on CRISPRi (clustered regularly interspaced short palindromic repeats interference) has emerged as a powerful tool for creating synthetic gene circuits, both in prokaryotes and in eukaryotes; yet, its lack of cooperativity has been pointed out as a potential obstacle for dynamic or multistable synthetic circuit construction. Here we use CRISPRi to build a synthetic oscillator ("CRISPRlator"), bistable network (toggle switch) and stripe pattern-forming incoherent feed-forward loop (IFFL). Our circuit designs, conceived to feature high predictability and orthogonality, as well as low metabolic burden and context-dependency, allow us to achieve robust circuit behaviors in Escherichia coli populations. Mathematical modeling suggests that unspecific binding in CRISPRi is essential to establish multistability. Our work demonstrates the wide applicability of CRISPRi in synthetic circuits and paves the way for future efforts towards engineering more complex synthetic networks, boosted by the advantages of CRISPR technology.
Pubmed
Open Access
Yes
Create date
08/01/2020 16:39
Last modification date
08/09/2020 6:23
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