PT  - JOURNAL ARTICLE
AU  - Hsin-Ho Huang
AU  - Yili Qian
AU  - Domitilla Del Vecchio
TI  - A quasi-integral controller for adaptation of genetic modules to variable ribosome demand
AID  - 10.1101/336271
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 336271
4099  - http://biorxiv.org/content/early/2018/06/01/336271.short
4100  - http://biorxiv.org/content/early/2018/06/01/336271.full
AB  - The behavior of genetic circuits is often poorly predictable. A gene’s expression level is not only determined by the intended regulators, but also largely dictated by changes in ribosome availability imparted by activation or repression of other genes. To address this problem, we design a quasiintegral biomolecular feedback controller that enables the expression level of any gene of interest (GOI) to adapt to changes in available ribosomes. The feedback is implemented through a synthetic small RNA (sRNA) that silences the GOI’s mRNA, and uses orthogonal extracytoplasmic function (ECF) sigma factor to sense the GOIs mRNA and to activate sRNA transcription. Without the controller, the expression level of the GOI is reduced by 50% when a resource competitor is activated. With the controller, by contrast, gene expression level is practically unaffected by the competitor. This feedback controller allows adaptation of genetic modules to variable ribosome demand and thus aids modular construction of complicated circuits.