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...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-04-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-58760-z |
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| _version_ | 1850181926638321664 |
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| 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 |
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