Tuning of Physiological Controller Motifs

Abstract

Genetic manipulation is increasingly used to fine tune organisms like bacteria and yeast for production of chemical compounds such as biofuels and pharmaceuticals. The process of creating the optimal organism is difficult as manipulation may destroy adaptation and compensation mechanisms that have been tuned by evolution to keep the organisms fit. The continued progress in synthetic biology depends on our ability to understand, manipulate, and tune these mechanisms. Concepts from control theory and control engineering are very applicable to these challenges. From a control theoretic viewpoint, disturbances rejection and set point tracking describe how adaptation mechanisms relate to perturbations and to signaling events. In this paper we investigate a set regulatory mechanisms in the form of biochemical reaction schemes, socalled controller motifs. We show how parameters related to the molecular and kinetic mechanisms influence on the dynamical behavior of disturbance rejection and set point tracking of each controller motif. This gives insight into how a molecular controller motif can be tuned to a specified regulatory response.

Structural identifiability of biomolecular controller motifs with and without flow measurements as model output

“…Different properties of controller motifs have been studied extensively, but to our knowledge and supported by an extensive literature search (see S1 Text), structural identifiability of controller motifs has so far not been investigated. Motivated by the fact that both dynamic and static performance of controller motifs are heavily affected by parameter values [26,[47][48][49], we investigate in this paper the structural identifiability of the so-called basic controller motifs [26] and the antithetic controller motifs [28,50].…”