Welcome to the new version of CaltechAUTHORS. Login is currently restricted to library staff. If you notice any issues, please email coda@library.caltech.edu
Published April 24, 2023 | Published + Supplemental Material
Journal Article Open

Addressable and adaptable intercellular communication via DNA messaging

Abstract

Engineered consortia are a major research focus for synthetic biologists because they can implement sophisticated behaviors inaccessible to single-strain systems. However, this functional capacity is constrained by their constituent strains' ability to engage in complex communication. DNA messaging, by enabling information-rich channel-decoupled communication, is a promising candidate architecture for implementing complex communication. But its major advantage, its messages' dynamic mutability, is still unexplored. We develop a framework for addressable and adaptable DNA messaging that leverages all three of these advantages and implement it using plasmid conjugation in E. coli. Our system can bias the transfer of messages to targeted receiver strains by 100- to 1000-fold, and their recipient lists can be dynamically updated in situ to control the flow of information through the population. This work lays the foundation for future developments that further utilize the unique advantages of DNA messaging to engineer previously-inaccessible levels of complexity into biological systems.

Additional Information

© The Author(s) 2023. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. We thank A. Halleran, A. Shur, and R. Williams for insightful discussions, and the members of the Murray lab for feedback on the manuscript. We also thank T. Dimitriu for providing plasmids from the F_(HR) system. Some of the schematic illustrations in this manuscript contain components adapted from the SBOL visual glyph library. This material is based upon work supported by the National Science Foundation Graduate Research Fellowship Program under Grant no. DGE-1745301 and by the Institute for Collaborative Biotechnologies through grants W911NF-09-D-0001 and W911NF-19-2-0026 from the U.S. Army Research Office. The content of the information in this report does not necessarily reflect the position or the policy of the Government, and no official endorsement should be inferred. Data availability: A description of all of the strains and constructs created for this study, as well as the GenBank accession IDs associated with their annotated sequences, can be found in Supplementary Data 1. Source data are provided in this paper. Code availability: Jupyter notebooks (written for Python 3.8.8) that use the Source Data to reproduce all of the analyses and data figures in this manuscript can be found at github.com/jpmarken/DNAmessaging or https://doi.org/10.5281/zenodo.7700530. Contributions: J.P.M. conceived and designed the project, performed the experiments, analyzed the data, and wrote the paper, all under the supervision of R.M.M. The authors declare no competing interests.

Attached Files

Published - s41467-023-37788-z.pdf

Supplemental Material - 41467_2023_37788_MOESM1_ESM.pdf

Supplemental Material - 41467_2023_37788_MOESM3_ESM.pdf

Supplemental Material - 41467_2023_37788_MOESM5_ESM.xlsx

Supplemental Material - 41467_2023_37788_MOESM6_ESM.xlsx

Files

41467_2023_37788_MOESM1_ESM.pdf
Files (2.6 MB)
Name Size Download all
md5:bef28af38b63c759efc075ef62da7440
16.2 kB Download
md5:2e9f9e28032c5bdb16af5b744e6d0f72
1.2 MB Preview Download
md5:ce1864672f7debeb4b70d78f567bc408
1.3 MB Preview Download
md5:3c80b3e09b787cd46ec054a15431e8a1
42.5 kB Preview Download
md5:095fc8d95591652810b11713de0bc6a1
32.1 kB Download

Additional details

Created:
August 22, 2023
Modified:
December 22, 2023