Diverse areas of biotechnology, including directed evolution, synthetic biology, and bioengineering, are impeded by a lack of general methods to link chemical and biochemical processes to output signals that can interact with the cell. While optical outputs, e.g. GFP and luciferase-based systems, are powerful for detection due to the minimally perturbative nature of light to biology, synthetic biology applications require the generation of signals that are <i>maximally</i> perturbative to the underlying biological system. To tackle this challenge, we are developing new classes of “biosensors” – protein-based detection systems that respond to defined input signals by producing versatile outputs. In one example, we have developed T7 RNAP-based biosensors to monitor and respond to molecular interactions, molecules, and external cues in live cells by the production of defined RNA outputs. As a second example. We have developed small molecule-generating biosensing systems that encode molecular interactions and other input signals in the generation of defined small molecule products in both <i>E. coli</i> and mammalian systems. We anticipate that our new biosensor systems will provide a simplified and robust strategy for engineering gene circuits for applications in screening, directed evolution, and synthetic biology.

Expanding the scope of biosensors: RNA- and small molecule-generating sensing systems

2019 Fall National Meeting

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