Engineering coupled consortia-based biosensors for diagnostic
Abstract Synthetic multicellular systems have great potential for performing complex tasks, including multi-signal detection and computation through cell-to-cell communication. However, engineering these systems is challenging, requiring precise control over the cell concentrations of distinct membe...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-04-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-58996-9 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850173015272194048 |
|---|---|
| author | Rongying Huang Valeriia Kravchik Rawan Zaatry Mouna Habib Naama Geva-Zatorsky Ramez Daniel |
| author_facet | Rongying Huang Valeriia Kravchik Rawan Zaatry Mouna Habib Naama Geva-Zatorsky Ramez Daniel |
| author_sort | Rongying Huang |
| collection | DOAJ |
| description | Abstract Synthetic multicellular systems have great potential for performing complex tasks, including multi-signal detection and computation through cell-to-cell communication. However, engineering these systems is challenging, requiring precise control over the cell concentrations of distinct members and coordination of their activity. Here, we develop a bacterial consortia-based biosensor for Heme and Lactate, wherein members are coupled through a global shared quorum-sensing signal that simultaneously controls the activity of the diverse biosensing strains. The multicellular system incorporates a gene circuit that computes the minimum between each biosensor’s activity and the shared signal. We evaluate three consortia configurations: one where the shared signal is externally supplied, another directly produced via an inducible gene circuit, and a third generated through an incoherent feedforward loop (IFFL) gene circuit. Among these configurations, the IFFL system, which maintains the shared signal at low and stable levels over an extended period, demonstrates improved performance and robustness against perturbations in cell populations. Finally, we examine these coupled consortia to monitor Lactate and Heme in humanized fecal samples for diagnostics. |
| format | Article |
| id | doaj-art-c6c341052e2f4d7eb701a35816fec307 |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-c6c341052e2f4d7eb701a35816fec3072025-08-20T02:19:57ZengNature PortfolioNature Communications2041-17232025-04-0116111410.1038/s41467-025-58996-9Engineering coupled consortia-based biosensors for diagnosticRongying Huang0Valeriia Kravchik1Rawan Zaatry2Mouna Habib3Naama Geva-Zatorsky4Ramez Daniel5Department of Biotechnology Technion—Israel Institute of Technology, Technion CityDepartment of Biomedical Engineering Technion—Israel Institute of Technology, Technion CityDepartment of Cell Biology and Cancer Science, Rappaport Technion Integrated Cancer Center (RTICC), Rappaport Faculty of Medicine, Technion – Israel Institute of TechnologyDepartment of Biomedical Engineering Technion—Israel Institute of Technology, Technion CityDepartment of Cell Biology and Cancer Science, Rappaport Technion Integrated Cancer Center (RTICC), Rappaport Faculty of Medicine, Technion – Israel Institute of TechnologyDepartment of Biomedical Engineering Technion—Israel Institute of Technology, Technion CityAbstract Synthetic multicellular systems have great potential for performing complex tasks, including multi-signal detection and computation through cell-to-cell communication. However, engineering these systems is challenging, requiring precise control over the cell concentrations of distinct members and coordination of their activity. Here, we develop a bacterial consortia-based biosensor for Heme and Lactate, wherein members are coupled through a global shared quorum-sensing signal that simultaneously controls the activity of the diverse biosensing strains. The multicellular system incorporates a gene circuit that computes the minimum between each biosensor’s activity and the shared signal. We evaluate three consortia configurations: one where the shared signal is externally supplied, another directly produced via an inducible gene circuit, and a third generated through an incoherent feedforward loop (IFFL) gene circuit. Among these configurations, the IFFL system, which maintains the shared signal at low and stable levels over an extended period, demonstrates improved performance and robustness against perturbations in cell populations. Finally, we examine these coupled consortia to monitor Lactate and Heme in humanized fecal samples for diagnostics.https://doi.org/10.1038/s41467-025-58996-9 |
| spellingShingle | Rongying Huang Valeriia Kravchik Rawan Zaatry Mouna Habib Naama Geva-Zatorsky Ramez Daniel Engineering coupled consortia-based biosensors for diagnostic Nature Communications |
| title | Engineering coupled consortia-based biosensors for diagnostic |
| title_full | Engineering coupled consortia-based biosensors for diagnostic |
| title_fullStr | Engineering coupled consortia-based biosensors for diagnostic |
| title_full_unstemmed | Engineering coupled consortia-based biosensors for diagnostic |
| title_short | Engineering coupled consortia-based biosensors for diagnostic |
| title_sort | engineering coupled consortia based biosensors for diagnostic |
| url | https://doi.org/10.1038/s41467-025-58996-9 |
| work_keys_str_mv | AT rongyinghuang engineeringcoupledconsortiabasedbiosensorsfordiagnostic AT valeriiakravchik engineeringcoupledconsortiabasedbiosensorsfordiagnostic AT rawanzaatry engineeringcoupledconsortiabasedbiosensorsfordiagnostic AT mounahabib engineeringcoupledconsortiabasedbiosensorsfordiagnostic AT naamagevazatorsky engineeringcoupledconsortiabasedbiosensorsfordiagnostic AT ramezdaniel engineeringcoupledconsortiabasedbiosensorsfordiagnostic |