Autonomous Bacterial Localization and Gene Expression Based on Nearby Cell Receptor Density
ARMY RESEARCH LAB ADELPHI MD SENSORS AND ELECTRON DEVICES DIRECTORATE
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Escherichia coli were genetically modified to enable programmed motility, sensing, and actuation based on the density of features on nearby surfaces. Then, based on calculated feature density, these cells expressed marker proteins to indicate phenotypic response. Specifically, site-specific synthesis of bacterial quorum sensing autoinducer-2 AI-2 is used to initiate and recruit motile cells. In our model system, we rewired E. colis AI-2 signaling pathway to direct bacteria to a squamous cancer cell line of head and neck SCCHN, where they initiate synthesis of a reporter drug surrogate based on a threshold density of epidermal growth factor receptor EGFR. This represents a new type of controller for targeted drug delivery as actuation synthesis and delivery depends on a receptor density marking the diseased cell. The ability to survey local surfaces and initiate gene expression based on feature density represents a new area-based switch in synthetic biology that will find use beyond the proposed cancer model here.
- Genetic Engineering and Molecular Biology
- Anatomy and Physiology
- Medicine and Medical Research