Subject: BioSim Discussion in Dresden, 20.12. From: Lutz Brusch Date: Tue, 20 Dec 2005 15:36:08 +0100 To: Femke Mensonides , Ursula Kummer , Martin Bertau CC: Lutz Brusch Dear Ursula, Femke, Martin and Lutz discussed the modelling steps in the BioSim context. New results by Martin implicate a rich biochemical network of stress response (about 25% of that are attached). In Dresden we so far concentrated on the kinetic model (extension of Sune's ful scale model) for anaerobioc conditions. The new network is hard to translate into a kinetic framework hence we now start a stoichiometric model in parallel. For both the kinetic and the stoichiometric model we need -stress response pathway -glycolysis + TCA + oxidative phosphorylation for which in the model setup phase -Dresden contributes the stress pathway (still under construction/discussion) and -Femke is giving more insight into NADH turnover under aerobic versus anaerobic, bacterial versus yeast conditions. As a temporal order we would first proceed with the stoichiometric model and then improve the kinetic model by pathways that turned out important in the elementary modes analysis (maybe using results from the Amsterdam workpackages? Femke will find out). Default assumptions for the stoichiometric model would be -Scenario A where a fixed percentage of TCA influx generates NADH for the biotransformation and stress response and -Scenario B where all NADH generated downstream is available for biotransformation and stress response. -Scenario C like in Pham et al. (attached) -Scenario D like in Rizzi et al. (attached) Our next tasks are: Martin theory: -assemble reaction network for degradation of xenobiotics and the stress response induced by it (incl. Glutathione) Martin exp: -12 data sets of flux distributions (D- and L-carbinol, EtOH and whatever will be suggested from the elementary modes analysis) for -3 different xenobiotic substrates -under aerobic versus anaerobic cond. -at high versus low glucose conc. For model setup: fed-batch exp. with different but fixed ketone concentration are needed. (Model then simulates the biotransformation with initial pulse of xenobiotic that is consumed over time.) Lutz theory: -setup reaction network in Copasi starting from stress response pathway assembled by Martin (pre-preliminary version attached) Femke theory: -compare 4 Scenarios for NADH turnover -compute the elementary modes with Copasi -interprete the elementary modes and compare with exp. flux distribution for D-carbinol, L-carbinol for different ketone conc. How to visually analyse the elementary modes? Is there an alternative to FluxAnalyser used in Heidelberg? Femke exp: -in Amsterdam use Martin's yeast and xenobiotics to determine CO2, EtOH flux and thereby the distribution between fermentation and respiration Greetings from Dresden, Femke(arrived in Dresden in time) and Lutz prelim_stress_pathway.gif Content-Type: image/gif Content-Encoding: base64 rizzi97.pdf Content-Type: application/pdf Content-Encoding: base64 AerobModelYeast.pdf Content-Type: application/pdf Content-Encoding: base64