title: External control of the GAL network in S. cerevisiae: a view from control theory.
abstract: While there is a vast literature on the control systems that cells utilize to regulate their own state, there is little published work on the formal application of control theory to the external regulation of cellular functions. This paper chooses the GAL network in S. cerevisiae as a well understood benchmark example to demonstrate how control theory can be employed to regulate intracellular mRNA levels via extracellular galactose. Based on a mathematical model reduced from the GAL network, we have demonstrated that a galactose dose necessary to drive and maintain the desired GAL genes' mRNA levels can be calculated in an analytic form. And thus, a proportional feedback control can be designed to precisely regulate the level of mRNA. The benefits of the proposed feedback control are extensively investigated in terms of stability and parameter sensitivity. This paper demonstrates that feedback control can both significantly accelerate the process to precisely regulate mRNA levels and enhance the robustness of the overall cellular control system.
authors.affiliation: Department of Mechanical, Aerospace and Biomedical Engineering, The University of Tennessee, Knoxville, Tennessee, United States of America.
authors.forename: Ruoting
authors.initials: R
authors.lastname: Yang
authors.forename: Scott C
authors.initials: SC
authors.lastname: Lenaghan
authors.forename: John P
authors.initials: JP
authors.lastname: Wikswo
authors.forename: Mingjun
authors.initials: M
authors.lastname: Zhang
mesh_terms: D019295:Computational Biology / Q000379:methods; D005246:Feedback; D005690:Galactose / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D053263:Gene Regulatory Networks; D007700:Kinetics; D008954:Models, Biological; D008957:Models, Genetic; D015233:Models, Statistical; D008962:Models, Theoretical; D012333:RNA, Messenger / Q000378:metabolism; D015203:Reproducibility of Results; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000502:physiology*
chemical_list: D012333:RNA, Messenger; D005690:Galactose