Stability analysis of the GAL regulatory network in Saccharomyces cerevisiae and Kluyveromyces lactis

BMC Bioinformatics

Research

Ganesh A Viswanathan¹  Pushkar Malakar¹  Venkatesh Kareenhalli¹  Vishwesh V Kulkarni²  Michael G Safonov³  Lucy Y Pao⁴ 

[1]Department of Chemical Engineering, Indian Institute of Technology Bombay, 400 076, Mumbai, India

[2]Department of Electrical Engineering, Indian Institute of Technology Bombay, 400 076, Mumbai, India

[3]Department of Electrical Engineering, University of Southern California, 90089-2563, Los Angeles, USA

[4]Department of Electrical, Computer, and Energy Engineering, University of Colorado, 80302, Boulder, CO, USA

关键词: Galactose;    Equilibrium Point;    Lactis;    Ordinary Differential Equation Model;    GAL4 Expression;   

DOI  :  10.1186/1471-2105-11-S1-S43

来源: Springer

【 摘 要 】

BackgroundIn the yeast Saccharomyces cerevisiae, interactions between galactose, Gal3p, Gal80p, and Gal4p determine the transcriptional status of the genes required for the galactose utilization. Increase in the cellular galactose concentration causes the galactose molecules to bind onto Gal3p which, via Gal80p, activates Gal4p, which induces the GAL3 and GAL80 gene transcription. Recently, a linear time-invariant multi-input multi-output (MIMO) model of this GAL regulatory network has been proposed; the inputs being galactose and Gal4p, and the outputs being the active Gal4p and galactose utilization. Unfortunately, this model assumes the cell culture to be homogeneous, although it is not so in practice. We overcome this drawback by including more biochemical reactions, and derive a quadratic ordinary differential equation (ODE) based model.ResultsWe show that the model, referred to above, does not exhibit bistability. We establish sufficiency conditions for the domain of attraction of an equilibrium point of our ODE model for the special case of full-state feedback controller. We observe that the GAL regulatory system of Kluyveromyces lactis exhibits an aberration of monotone nonlinearity and apply the Rantzer multipliers to establish a class of stabilizing controllers for this system.ConclusionFeedback in a GAL regulatory system can be used to enhance the cellular memory. We show that the system can be modeled as a quadratic nonlinear system for which the effect of feedback on the domain of attraction of the equilibrium point can be characterized using linear matrix inequality (LMI) conditions that are easily implementable in software. The benefit of this result is that a mathematically sound approach to the synthesis of full-state and partial-state feedback controllers to regulate the cellular memory is now possible, irrespective of the number of state-variables or parameters of interest.

【 授权许可】

CC BY   
© Kulkarni et al; licensee BioMed Central Ltd. 2010