Optimal genetic circuit design for mammalian synthetic biology applications

Synthetic biology combines biology and engineering to redesign living organisms by conferring them new properties. Synthetic biologists harness the power of nature to solve problems in medicine, manufacturing, and agriculture and use engineering principles to control and perturb cell pathways to gather novel insights into biological functions. Specifically, the programming of new functions into mammalian cells has tremendous application in research and medicine. The rapid advances in the ability to synthesize DNA and RNA have increased our understanding of gene function and regulation and have enabled the expansion of genetic parts available for programming cell biology. Genetic parts can be multiplexed to build complex genetic circuits to (i) confer new functions to the host cells, (ii) regulate endogenous pathways, or (iii) sense inputs of interest to actuate a cellular response. This thesis focuses on the optimization of genetic circuit design for mammalian synthetic biology applications. It covers the need for additional regulatory tools for tight spatiotemporal control of gene expression and cell response and the need for a better understanding of how regulation processes work in cells. Finally, it explores strategies to select biologically relevant inputs for sensor-actuator devices that control cell fate.