IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v11y2020i1d10.1038_s41467-020-16574-1.html
   My bibliography  Save this article

Multistable and dynamic CRISPRi-based synthetic circuits

Author

Listed:
  • Javier Santos-Moreno

    (University of Lausanne)

  • Eve Tasiudi

    (ETH Zurich and SIB Swiss Institute of Bioinformatics)

  • Joerg Stelling

    (ETH Zurich and SIB Swiss Institute of Bioinformatics)

  • Yolanda Schaerli

    (University of Lausanne)

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.

Suggested Citation

  • Javier Santos-Moreno & Eve Tasiudi & Joerg Stelling & Yolanda Schaerli, 2020. "Multistable and dynamic CRISPRi-based synthetic circuits," Nature Communications, Nature, vol. 11(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16574-1
    DOI: 10.1038/s41467-020-16574-1
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-020-16574-1
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-020-16574-1?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Javier Santos-Moreno & Eve Tasiudi & Hadiastri Kusumawardhani & Joerg Stelling & Yolanda Schaerli, 2023. "Robustness and innovation in synthetic genotype networks," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Jung Hun Park & Gábor Holló & Yolanda Schaerli, 2024. "From resonance to chaos by modulating spatiotemporal patterns through a synthetic optogenetic oscillator," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    3. Ankush Auradkar & Annabel Guichard & Saluja Kaduwal & Marketta Sneider & Ethan Bier, 2023. "tgCRISPRi: efficient gene knock-down using truncated gRNAs and catalytically active Cas9," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    4. Yuanli Gao & Lei Wang & Baojun Wang, 2023. "Customizing cellular signal processing by synthetic multi-level regulatory circuits," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    5. William M. Shaw & Lucie Studená & Kyler Roy & Piotr Hapeta & Nicholas S. McCarty & Alicia E. Graham & Tom Ellis & Rodrigo Ledesma-Amaro, 2022. "Inducible expression of large gRNA arrays for multiplexed CRISPRai applications," Nature Communications, Nature, vol. 13(1), pages 1-10, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16574-1. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.