Design of genetic circuits that are robust to resource competition

• Main Authors: McBride, Cameron David (Author), Grunberg, Theodore Wu (Author), Del Vecchio, Domitilla (Author)
• Other Authors: Massachusetts Institute of Technology. Department of Mechanical Engineering (Contributor), Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science (Contributor)
• Format: Article
• Language: English
• Published: Elsevier BV, 2022-01-13T14:26:47Z.
• Subjects: Article
• Online Access: Get fulltext

 The ability to engineer genetic circuits in living cells has tremendous potential in many applications, from health, to energy, to bio-manufacturing. Although substantial efforts have gone into design approaches that make circuits robust to variable cellular context, context dependence of genetic circuits remains a significant hurdle. We review intra-cellular resource competition, one culprit of context dependence, and summarize recent efforts toward design approaches to mitigate it. We classify these approaches into two main groups: global control and local control. In the former, the pool of resources is regulated to meet the demand, and in the latter, individual modules are regulated to be robust to variability in the pool of resources. Within each group, we highlight both feedback and feedforward implementations.