Engineering intercellular communication using M13 phagemid and CRISPR-based gene regulation for multicellular computing in Escherichia coli

Abstract Engineering multicellular consortia, where information processing is distributed across specialized cell types, offers a promising strategy for implementing sophisticated biocomputing systems. However, a major challenge remains in establishing orthogonal intercellular communication, or “wir...

Full description

Saved in:
Bibliographic Details
Main Authors: Hadiastri Kusumawardhani, Florian Zoppi, Roberto Avendaño, Yolanda Schaerli
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-58760-z
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850181926638321664
author Hadiastri Kusumawardhani
Florian Zoppi
Roberto Avendaño
Yolanda Schaerli
author_facet Hadiastri Kusumawardhani
Florian Zoppi
Roberto Avendaño
Yolanda Schaerli
author_sort Hadiastri Kusumawardhani
collection DOAJ
description Abstract Engineering multicellular consortia, where information processing is distributed across specialized cell types, offers a promising strategy for implementing sophisticated biocomputing systems. However, a major challenge remains in establishing orthogonal intercellular communication, or “wires,” within synthetic bacterial consortia. In this study, we address this bottleneck by integrating phagemid-mediated intercellular communication with CRISPR-based gene regulation for multicellular computing in synthetic E. coli consortia. We achieve intercellular communication with high sensitivity by regulating the transfer of single guide RNAs (sgRNAs) encoded on M13 phagemids from sender to receiver cells. Once inside the receiver cells, the transferred sgRNAs mediate gene regulation via CRISPR interference. Leveraging this approach, we successfully constructed one-, two-, and four-input logic gates. Our work expands the toolkit for intercellular communication and paves the way for complex information processing in synthetic microbial consortia, with diverse potential applications, including biocomputing, biosensing, and biomanufacturing.
format Article
id doaj-art-dca625fb94fa428eaaad32cabfe37bb1
institution OA Journals
issn 2041-1723
language English
publishDate 2025-04-01
publisher Nature Portfolio
record_format Article
series Nature Communications
spelling doaj-art-dca625fb94fa428eaaad32cabfe37bb12025-08-20T02:17:48ZengNature PortfolioNature Communications2041-17232025-04-0116111310.1038/s41467-025-58760-zEngineering intercellular communication using M13 phagemid and CRISPR-based gene regulation for multicellular computing in Escherichia coliHadiastri Kusumawardhani0Florian Zoppi1Roberto Avendaño2Yolanda Schaerli3Department of Fundamental Microbiology, Faculty of Biology and Medicine, University of LausanneDepartment of Fundamental Microbiology, Faculty of Biology and Medicine, University of LausanneDepartment of Fundamental Microbiology, Faculty of Biology and Medicine, University of LausanneDepartment of Fundamental Microbiology, Faculty of Biology and Medicine, University of LausanneAbstract Engineering multicellular consortia, where information processing is distributed across specialized cell types, offers a promising strategy for implementing sophisticated biocomputing systems. However, a major challenge remains in establishing orthogonal intercellular communication, or “wires,” within synthetic bacterial consortia. In this study, we address this bottleneck by integrating phagemid-mediated intercellular communication with CRISPR-based gene regulation for multicellular computing in synthetic E. coli consortia. We achieve intercellular communication with high sensitivity by regulating the transfer of single guide RNAs (sgRNAs) encoded on M13 phagemids from sender to receiver cells. Once inside the receiver cells, the transferred sgRNAs mediate gene regulation via CRISPR interference. Leveraging this approach, we successfully constructed one-, two-, and four-input logic gates. Our work expands the toolkit for intercellular communication and paves the way for complex information processing in synthetic microbial consortia, with diverse potential applications, including biocomputing, biosensing, and biomanufacturing.https://doi.org/10.1038/s41467-025-58760-z
spellingShingle Hadiastri Kusumawardhani
Florian Zoppi
Roberto Avendaño
Yolanda Schaerli
Engineering intercellular communication using M13 phagemid and CRISPR-based gene regulation for multicellular computing in Escherichia coli
Nature Communications
title Engineering intercellular communication using M13 phagemid and CRISPR-based gene regulation for multicellular computing in Escherichia coli
title_full Engineering intercellular communication using M13 phagemid and CRISPR-based gene regulation for multicellular computing in Escherichia coli
title_fullStr Engineering intercellular communication using M13 phagemid and CRISPR-based gene regulation for multicellular computing in Escherichia coli
title_full_unstemmed Engineering intercellular communication using M13 phagemid and CRISPR-based gene regulation for multicellular computing in Escherichia coli
title_short Engineering intercellular communication using M13 phagemid and CRISPR-based gene regulation for multicellular computing in Escherichia coli
title_sort engineering intercellular communication using m13 phagemid and crispr based gene regulation for multicellular computing in escherichia coli
url https://doi.org/10.1038/s41467-025-58760-z
work_keys_str_mv AT hadiastrikusumawardhani engineeringintercellularcommunicationusingm13phagemidandcrisprbasedgeneregulationformulticellularcomputinginescherichiacoli
AT florianzoppi engineeringintercellularcommunicationusingm13phagemidandcrisprbasedgeneregulationformulticellularcomputinginescherichiacoli
AT robertoavendano engineeringintercellularcommunicationusingm13phagemidandcrisprbasedgeneregulationformulticellularcomputinginescherichiacoli
AT yolandaschaerli engineeringintercellularcommunicationusingm13phagemidandcrisprbasedgeneregulationformulticellularcomputinginescherichiacoli