Tuning and functionalization of logic gates for time resolved programming of bacterial populations
Year: 2024
Type: article
Abstract: In order to increase our command over genetically engineered bacterial populations in bioprocessing and therapy, synthetic regulatory circuitry needs to enable the temporal programming of a number of consecutive functional tasks without external interventions. In this context, we have engineered a genetic circuit encoding an autonomous but chemically tunable timer in Escherichia coli, based on the concept of a transcription factor cascade mediated by the cytoplasmic dilution of repressors. As proof-of-concept, we used this circuit to impose a time-resolved two-staged synthetic pathway composed of a production-followed-by-lysis program, via a single input. Moreover, via a recombinase step, this synchronous timer was further engineered into an asynchronous timer in which the generational distance of differentiating daughter cells spawning off from a stem-cell like mother cell becomes a predictable driver and proxy for timer dynamics. Using this asynchronous timer circuit, a temporally defined population heterogeneity can be programmed in bacterial populations.
Source: Nucleic Acids Research
DOI: 10.1093/nar/gkae1158
Institution: KU Leuven
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,192
Awards: Reprogramming bacterial bioreactor populations using a synthetic phage chassis, G4357437082, Next-generation bioprocess engineering: phage-based synthetic reprogramming of bacterial bioreactor populations, Phage Transmission Strategies, Synthetic Transduction as a Novel Tool for Population Programming
OpenAlex ID: W4405220611