title: Mathematical model of galactose regulation and metabolic consumption in yeast.
abstract: The galactose network has been extensively studied at the unicellular level to broaden our understanding of the regulatory mechanisms governing galactose metabolism in multicellular organisms. Although the key molecular players involved in the metabolic and regulatory processes of this system have been known for decades, their interactions and chemical kinetics remain incompletely understood. Mathematical models can provide an alternative method to study the dynamics of this network from a quantitative and a qualitative perspective. Here, we employ this approach to unravel the main properties of the galactose network, including equilibrium binary and temporal responses, as a way to decipher its adaptation to actively-changing inputs. We combine its two main components: the genetic branch, which allows for bistable responses, and a metabolic branch, encompassing the relevant metabolic processes that can be repressed by glucose. We use both computational tools to estimate model parameters based on published experimental data, as well as bifurcation analysis to decipher the properties of the system in various parameter regimes. Our model analysis reveals that the interplay between the inducer (galactose) and the repressor (glucose) creates a bistable regime which dictates the temporal responses of the system. Based on the same bifurcation techniques, we explain why the system is robust to genetic mutations and molecular instabilities. These findings may provide experimentalists with a theoretical framework with which they can determine how the galactose network functions under various conditions.
authors.affiliation: Department of Mathematics, McGill University, Montreal, Quebec, Canada.
authors.forename: Tina M
authors.initials: TM
authors.lastname: Mitre
authors.affiliation: Department of Mathematics, McGill University, Montreal, Quebec, Canada; Department of Physiology, McGill University, Montreal, Quebec, Canada; Centre for Nonlinear Dynamics, Montreal, Quebec, Canada.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Mackey
authors.affiliation: Department of Mathematics, McGill University, Montreal, Quebec, Canada; Department of Physiology, McGill University, Montreal, Quebec, Canada; Centre for Nonlinear Dynamics, Montreal, Quebec, Canada. Electronic address: anmar.khadra@mcgill.ca.
authors.forename: Anmar
authors.initials: A
authors.lastname: Khadra
mesh_terms: D049109:Cell Proliferation; D005690:Galactose / Q000378:metabolism*; D007700:Kinetics; D053858:Metabolic Networks and Pathways / Q000235:genetics; D008954:Models, Biological; D018085:Regulon / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D013997:Time Factors
chemical_list: D005690:Galactose
keywords: Environmental adaptation; Galactose gene-regulatory network; Glucose repression of galactose metabolism; Leloir pathway; Mathematical model