Wed, 08/11/2017 - 16:15
,
Campus SB, E2 6, Room E04

Prof. Dr. Roberto Mulet
(
Host: Prof. Dr. Ludger Santen
)
Physics Faculty, University of Havana, Cuba

Characterizing steady states of genome-scale metabolic networks in continuous cell cultures

In this talk I will present a model for continuous cell culture coupling intra-cellular metabolism to extracellular variables of a bioreactor taking into account the growth capacity of the cell and the impact of toxic byproduct accumulation. We provide a method to determine the steady states of this system that is tractable for metabolic networks of arbitrary complexity. We demonstrate our approach in a toy model and in a genome-scale metabolic network of the Chinese hamster ovary cell line. We will present a number of consequences from the model that are independent of parameter values. First, that the ratio between cell density and dilution rate is an ideal control parameter to fix a steady state with desired metabolic properties invariant across perfusion systems.  Second, invariance laws between continuous cell cultures with different parameters. Moreover, from our simulations emerge a complex landscape of steady states in continuous cell culture, including multiple metabolic switches, which also explain why cell-line and media benchmarks carried out in batch culture cannot be extrapolated to perfusion. A practical consequence of our results is that the chemostat is an ideal experimental model for large-scale high-density perfusion cultures, where the complex landscape of metabolic transitions is faithfully reproduced.

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