title: Using computational modeling and experimental synthetic perturbations to probe biological circuits.
abstract: This chapter describes approaches for using computational modeling of synthetic biology perturbations to analyze endogenous biological circuits, with a particular focus on signaling and metabolic pathways. We describe a bottom-up approach in which ordinary differential equations are constructed to model the core interactions of a pathway of interest. We then discuss methods for modeling synthetic perturbations that can be used to investigate properties of the natural circuit. Keeping in mind the importance of the interplay between modeling and experimentation, we next describe experimental methods for constructing synthetic perturbations to test the computational predictions. Finally, we present a case study of the p53 tumor-suppressor pathway, illustrating the process of modeling the core network, designing informative synthetic perturbations in silico, and testing the predictions in vivo.
authors.affiliation: Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 10, Room B1B42, 10 Center Dr., MSC 1500, Bethesda, MD, 20892, USA.
authors.forename: Joshua R
authors.initials: JR
authors.lastname: Porter
authors.forename: Eric
authors.initials: E
authors.lastname: Batchelor
mesh_terms: D019295:Computational Biology / Q000379:methods*; D058615:Synthetic Biology / Q000379:methods*; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D016159:Tumor Suppressor Protein p53