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Vortrag von Prof. Dr. Uwe Sauer im Rahmen unserer ZBI "Distinguished Speaker Series"

Am Mittwoch, 20. Juni 2012 wird Prof. Dr. Uwe Sauer (ETH Zürich, Institute of Molecular Systems Biology) im Rahmen der ZBI "Distinguished Speaker Series" einen Vortrag zum Thema "Identification of allosteric and transcriptional regulation that controls metabolic function" halten (Raum 001, ZBI (Gebäude E 2.1); Beginn: Punkt 17:00 Uhr).



After about ten years of research renaissance in metabolism, the present challenge is to understand how metabolic fluxes are controlled by a complex interplay of overlapping regulatory mechanisms (1). Reconstruction of various regulatory network topologies is steaming, but we struggle with understanding how the many regulation events are integrated into functional outputs. For metabolism, this functional output is the traffic of small molecules to fuel growth and energy requirements and can be quantified through 13C-flux analysis (2). By integrating a large dynamic data set on a seemingly simply nutritional adaption of the bacterium B. subtilis with various computational methods, I will illustrate how we delineated the actively controlling regulation events from the much larger number of co-occurring regulation events (3). Based on 13C-flux data from large-scale deletion experiments of transcription factors in different microbes, I will then show how we identify the surprisingly small number of these genetic regulators that are involved in controlling the distribution of flux in the network (4, 5). A major knowledge gap – both topologically and functionally - resides in the regulatory network of protein-metabolite interactions, simply because we lacked pertinent methods for systematic analyses. To address this problem I will present out new experimental/computational approach to identify in vivo active allosteric regulation of enzyme activity from short-term dynamics of intracellular metabolites. The presented, and other data underline the conceptual shift in our perception of metabolism from an engine of cellular operation to a generator of input and feedback signals for regulatory circuits that govern many important decisions on cell proliferation, differentiation, death, and naturally metabolism (6).



1.             Gerosa L & Sauer U. Curr. Opin. Biotechnol. 22: 566 (2011)

2.             Sauer U. Mol Sys. Biol. 2: 62 (2006)

3.             Buescher J et al. Science 335: 1099 (2012)

4.             Fendt, Olivera, Christen, Picotti, Dechant & Sauer. Mol Sys. Biol. 6: 432 (2010)

5.             Haverkorn, Nanchen, Nallet, Kleijn & Sauer. Mol Sys. Biol. 7: 477 (2011)

6.             Heinemann M & Sauer U. Curr. Opin. Microbiol. 13: 337 (2010).