RT Journal Article SR Electronic T1 Engineered gene circuits with reinforcement learning allow bacteria to master gameplaying JF bioRxiv FD Cold Spring Harbor Laboratory SP 2022.04.22.489191 DO 10.1101/2022.04.22.489191 A1 Adrian Racovita A1 Satya Prakash A1 Clenira Varela A1 Mark Walsh A1 Roberto Galizi A1 Mark Isalan A1 Alfonso Jaramillo YR 2022 UL http://biorxiv.org/content/early/2022/04/25/2022.04.22.489191.abstract AB The engineering of living cells able to learn algorithms by themselves, such as playing board games —a classic challenge for artificial intelligence— will allow complex ecosystems and tissues to be chemically reprogrammed to learn complex decisions. However, current engineered gene circuits encoding decision-making algorithms have failed to implement self-programmability and they require supervised tuning. We show a strategy for engineering gene circuits to rewire themselves by reinforcement learning. We created a scalable general-purpose library of Escherichia coli strains encoding elementary adaptive genetic systems capable of persistently adjusting their relative levels of expression according to their previous behavior. Our strains can learn the mastery of 3×3 board games such as tic-tac-toe, even when starting from a completely ignorant state. We provide a general genetic mechanism for the autonomous learning of decisions in changeable environments.One-Sentence Summary We propose a scalable strategy to engineer gene circuits capable of autonomously learning decision-making in complex environments.Competing Interest StatementThe authors have declared no competing interest.