Sarah-Maria Fendt, Robert Schutz, Paula Picotti, Ruedi Aebersold, Nicola Zamboni

& Uwe Sauer

Institute of Molecular Systems Biology, ETH Zurich

To understand how complex networks respond to genetic or environmental challenges is one of the key challenges of systems biology. Great strides have been made in our ability to monitor transcriptional and proteome responses. Within metabolism, recent technological advances in MS-based metabolomics and 13C-flux analysis provide us with experimental methods to assess the functional state and output of large enzyme reaction networks (1). Using our mini-scale 13C-flux (2), high-throughput metabolomics, and targeted proteomics, we quantify here global functional responses of yeast metabolism. In particular we focus on unravelling the active network of transcriptional regulation that actually controls the distribution of metabolic fluxes under different environmental conditions.

The growing body of available flux data allows now to test whether the detected flux distributions arise from general principles of network organization and operation (3). In particular, we will discuss what kind of optimality principle (and their shortcoming) can be invoked to approximate the intracellular flux distribution on the basis of stoichiometric network models and flux balance analysis.

1. Sauer, U. Mol. Sys. Biol. 2, 62-68 (2006).

2. Fischer, E. & Sauer, U. Nat. Genet. 37, 636-640 (2005).

3. Schütz, R., Küpfer, L & Sauer, U. Mol Sys. Biol. 3, 119 (2007).

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