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Published March 17, 2023 | Supplemental Material + Submitted
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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 in a plasmid conjugation-based communication channel. Our system can bias the transfer of messages to targeted receiver strains by 100-to 1000-fold, and their recipient lists can be dynamically updatedin situto 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 copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license. 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 FHR system. 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. Author Contributions. J.P.M. conceived and designed the project, performed the experiments, analyzed the data, and wrote the manuscript, all under the supervision of R.M.M. Data and Strain Availability. Raw data for CFU counts can be found in the Supplementary Materials. As of this writing, strains and plasmids created for this study are being prepared for deposition to AddGene. Sequence maps for the constructs created for this study are available upon request. The authors have declared no competing interest.

Attached Files

Submitted - 2022.11.17.516988v1.full.pdf

Supplemental Material - media-1.xlsx

Supplemental Material - media-2.xlsx

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Additional details

Created:
August 20, 2023
Modified:
December 13, 2023