CAREER: Deciphering and Engineering Biological State Machines with Synthetic Biology

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Biology is full of rich and complex systems where the interplay between past events, present inputs, and genetics determines cellular behavior. For example, stem cells are in a pluripotent "state" in which they can self-renew and also transform into diverse cell types with distinct functions, such as skin, bone, and blood cells, based on the timing and identities of regulatory signals. These properties require cells to store memory and perform computations, similar to modern computers. To understand such systems, the investigator proposes that biological systems can be thought of as state machines, in which the identity and function of a cell as well as transitions between these cell "states" are determined by past events and present inputs. The research team will build synthetic gene circuits that implement artificial biological state machines along with algorithms to guide their design. The research team will experiment on these circuits to quantify and gain insights into their behavior.BROADER IMPACTS. To ensure broad impacts, the investigator will establish a new course called Biological Circuit Engineering Laboratory (BioCEL) to educate interdisciplinary scientists at the intersection of biology and engineering and will provide these teaching materials openly to the public. Furthermore, the investigator will engage high school, community college, and university students with opportunities for hands-on research. The investigator will create competitive games that teach the concepts used in this research to the general public. Finally, the investigator will establish an online resource to share the algorithms and circuits developed in this project to encourage their use by the broader scientific community. The creation of new design strategies for biological state machines is expected to shed insights into natural biological systems and advance important basic science, biotechnology, and biosensing applications.