University of California, San Francisco
San Francisco, CA
Detecting signals (“sensing”) and responding to them (“actuating”) are among the most fundamental abilities of living systems. This project aims to engineer new sensor/actuator systems that go beyond what exists in nature. Natural sensor/actuators can regulate very complex biological behaviors, such as production of chemicals in metabolism, formation of microbial communities in the human gut, or differentiation of cells in mammalian tissues. To be able to probe and precisely control such behavior, but not be limited to existing signals, would transform biological engineering and cell biology. The team proposes to develop a platform technology to computationally engineer proteins that convert sensing of small molecule signals into responses in living cells. Keck funding will allow them to fundamentally advance their ability to engineer such new biological functions by (i) inventing robotics-inspired approaches to reshape proteins for sensing new signals and (ii) optimizing the resulting designs to function in cells. The team’s results will enable them to begin to realize the enormous potential of engineered new sensor/actuators in testbed applications, including: (i) manufacturing valuable chemicals in microbes, (ii) building sensor/actuators that control communities of cells, and (iii) probing biology, where sensor/actuators would allow study of processes causing cancer and inflammation in new ways.
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