While there has been significant progress in the development of engineering principles for synthetic biology, a substantial challenge is the construction of robust circuits in a noisy cellular environment. Such an environment leads to considerable intercellular variability in circuit behavior, which can hinder functionality at the colony level. Here, we engineer the synchronization of thousands of oscillating colony “biopixels” over centimetre length scales through the use of synergistic intercellular coupling involving quorum sensing within a colony and gas-phase redox signaling between colonies. We use this platform to construct an LCD-like macroscopic clock that can be used to sense arsenic via modulation of the oscillatory period. Given the repertoire of sensing capabilities of bacteria such as E. coli, the ability to coordinate their behavior over large length scales sets the stage for the construction of low cost genetic biosensors that are capable of detecting heavy metals and pathogens in the field.
Synthetic biology has rapidly progressed over the past decade and is now positioned to impact important problems in health and energy. In the clinical arena, the field has thus far focused primarily on the use of bacteria and bacteriophages to overexpress therapeutic gene products. The next generation of multigene circuits will control the triggering, amplitude, and duration of therapeutic activity in vivo. This will require a host organism that is easy to genetically modify, leverages existing successful circuit designs, and has the potential for use in humans. Here, we show that gene circuits that were originally constructed and tested in Escherichia coli translate to Salmonella typhimurium, a therapeutically relevant microbe with attenuated strains that have exhibited safety in several human clinical trials. These strains are essentially nonvirulent, easy to genetically program, and specifically grow in tumor environments. Developing gene circuits on this platform could enhance our ability to bring sophisticated genetic programming to cancer therapy, setting the stage for a new generation of synthetic biology in clinically relevant microbes.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.