BACK TO INDEX
Publications of Eduardo D. Sontag jointly with M.L. Gennaro
Articles in journal or book chapters
and O.A. Igoshin.
Non-monotonic response dynamics of glyoxylate shunt genes in Mycobacterium tuberculosis.
PLoS Computational Biology,
Understanding how dynamical responses of biological networks are constrained by underlying network topology is one of the fundamental goals of systems biology. Here we employ monotone systems theory to formulate a theorem stating necessary conditions for non-monotonic time-response of a biochemical network to a monotonic stimulus. We apply this theorem to analyze the non-monotonic dynamics of the sigmaB-regulated glyoxylate shunt gene expression in Mycobacterium tuberculosis cells exposed to hypoxia. We first demonstrate that the known network structure is inconsistent with observed dynamics. To resolve this inconsistency we employ the formulated theorem, modeling simulations and optimization along with follow-up dynamic experimental measurements. We show a requirement for post-translational modulation of sigmaB activity in order to reconcile the network dynamics with its topology. The results of this analysis make testable experimental predictions and demonstrate wider applicability of the developed methodology to a wide class of biological systems.
BACK TO INDEX
This material is presented to ensure timely dissemination of
scholarly and technical work. Copyright and all rights therein
are retained by authors or by other copyright holders.
Last modified: Tue Jun 30 22:40:29 2020
This document was translated from BibTEX by