Using Computational Modeling and Experimental Synthetic Perturbations to Probe Biological Circuits

Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1244)

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.

Key words

Synthetic biology Dynamical systems Computational modeling Experimental design Signal transduction Metabolism 

Notes

Acknowledgment

This work was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health.

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Laboratory of Pathology, Center for Cancer Research, National Cancer InstituteNational Institutes of HealthBethesdaUSA

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