Construction of robust, multi-input genetic circuits linked with feedback loops
Tatenda Shopera, William R. Henson, Young Je Lee, Kenneth Ng, Andrew Ng, and Tae Seok Moon
Washington University in Saint Louis
Saint Louis, MO
The ability to program living cells with novel functions has great potential to unlock important innovative solutions to many industrial, medical, and energy challenges. For example, artificial gene networks have been engineered in organisms to produce products ranging from pharmaceuticals to biofuels. However, many applications are yet to be fully exploited due to poor understanding of how robust, reliable, and predictable complex genetic networks are constructed. Thus, understanding the underlying design strategies implemented by natural biological systems to execute reliable behavior is essential for programming complex cellular functions. Our overarching goal is to determine the governing design principles of biological robustness by building simple genetic circuits from the bottom-up. Among these circuits, we have successfully constructed noise-tolerant bistable switches by combining multiple-protein interactions (regulatory cascades) and feedback systems using biological parts obtained from nature. Specifically, in this presentation, we will highlight how microorganisms were programmed to retain strong memory over a wide range of input signals in a predictable manner through engineering of the gene regulatory architecture.