Leading PI: Shriskrishnan Sankaran
Living therapeutic materials developed by the LSC will target both easily accessible tissues like the eye and harder-to-reach tissues such as the lung or liver. Controlling bacterial activity through an externally applied trigger is desirable for these scenarios. Temperature is an attractive trigger due to the body’s tight regulation of its temperature, which can be manipulated both externally and internally. Genetic switches in E. coli, based on temperature-sensitive transcriptional repressors, have been developed to achieve thermally regulated gene expression across various temperature ranges (32°C – 36°C, 36°C – 38°C, 42°C – 46°C). These temperature ranges can be achieved through contact heating (e.g., heat compress, hot air) or infrared irradiation for peripheral applications, and focused ultrasound for deep-tissue therapies.
This proposal aims to adapt these thermal bioswitches in ClearColi for the production of the anti-inflammatory proteins, the antibiotic Darobactin in collaboration with HIPS, and Ectoine in collaboration with iSBio. The different therapeutics involved in this project could address medical conditions such as chronic inflammations, infections, allergic reactions, malignant tumors, and mucosal dryness.
Related Publications:
Dey S, Seyfert CE, Fink-Straube C, Kany AM, Müller R, Sankaran S. Thermo-amplifier circuit in probiotic E. coli for stringently temperature-controlled release of a novel antibiotic. J Biol Eng. 2024 Nov 12;18(1):66. doi: 10.1186/s13036-024-00463-y. PMID: 39533331; PMCID: PMC11559228
Dey S, Sankaran S. Engineered bacterial therapeutics with material solutions. Trends Biotechnol. 2024 Dec;42(12):1663-1676. doi: 10.1016/j.tibtech.2024.06.011. Epub 2024 Jul 18. PMID: 39030122.