On the design of integral translational resource allocation controllers for synthetic cellular circuitry

Competition for gene expression resources within cellular systems limits the modularity of synthetic circuits, and can lead to the emergence of hidden regulatory interactions between different circuit genes. Experimental evidence suggests that the finite number of free ribosomes in the cell limits protein synthesis capacity and can create unforeseen coupling between co-expressed circuit genes that can result in performance degradation or even circuit failure. Recent work has shown that the cell's ribosome population can be subdivided into host-specific and circuit-specific functions by the production of quasi-orthogonal ribosomes. In this paper, we investigate the design of an integral feedback controller which acts to dynamically allocate ribosomes between host and circuit genes in order to reduce circuit-circuit coupling. We show that whilst the controller is able to successfully allocate resources and improve circuit performance, a non-zero steady state error remains. We show that interactions between the host cell's physiology and the synthetic circuitry act to prevents perfect integral action for the proposed controller architecture.