Stoichiometric constraint-based modelling of the yeast metabolic oscillator

Douglas Brian MURRAY

Institute for Advanced Biosciences, Keio University, JP


   The metabolic network is the primary driver for cellular dynamics. The vast majority of research has focussed on isolated sub-systems of the metabolic network, leading to great advances in our understanding of their biochemical and genetic regulation of these sub-systems. Bakers' yeast has been at the forefront of this research, leading to perhaps the most comprehensive biochemical network model for any organism[1]. However, our holistic understanding of metabolic dynamics remains poor, partly because of the mushrooming complexity of biochemical systems. Our group primarily uses the autonomous metabolic oscillator that emerges during continuously grown yeast cultures to probe cellular dynamics in precisely defined environments[2,3]. During the oscillation the cell-division cycle[4,5], metabolome[6,7], transcriptome[5,8,9] and chromatin state[1012] show specific phase relationships with respiratory activity. Here, I will present our efforts to integrating these data with dynamical constraint-based modelling, specifically a dynamical Flux Balance Analysis (Shüki FBA). I will elaborate on the self-organisation of catabolism and anabolism, the under appreciated role for carbon dioxide fixation in yeast, methods to predict the temporal profiles of metabolites, and future directions and challenges for modelling dynamical systems.



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