Thomas Millat

BaCell-SysMO 2 Modelling carbon core metabolism in Bacillus subtilis – Exploring the contribution of protein complexes in core carbon and nitrogen metabolism.

Bacillus subtilis is a prime model organism for systems biology approaches because it is one of the most advanced models for functional genomics. Furthermore, comprehensive information on cell and molecular biology, physiology and genetics is available and the European Bacillus community (BACELL) has a well-established reputation for applying ...

Systems Biology of Clostridium acetobutylicum - a possible answer to dwindling crude oil reserves

Here, we use hyperbolic tangents to fit experimental data of AB fermentation in C. acetobutylicum in continous culture at steady state for different external pHs. The estimated parameters are used to define acidogenic and solventogenic phase. Furthermore, an transition phase is identified which cannot be assigned to acidogenesis or solventogenesis.

Several plots compare the fits to the experimental data.

This function estimates the parameters of growth functions of the acid-forming and solvent-forming population observed in 'forward'-shift experiments of phosphate-limited continuous cultures of C. acetobutylicum. The parameters are used in the 'Two-Populations'-Model of the pH-induced metabolic shift.

It assumed that the found behaviour of the optical density during these experiments results from a phenotypic switch caused by the changing pH level.

This model assumes a phenotypic switch between an acid- and solvent-forming population caused by the changing pH levels. The two phenotypes differ in their transcriptomic, proteomic, and ,thus, their metabolomic profile. Because the growth rates of these phenotypes depends on the extracellular pH, the initiation of the pH-shift results in a significant decline of the acidogenic population. Simultaneously, the solvent-forming population rises and establishes an new steady state.

The model is build ...

The fitted function describes the pH-drop during 'forward'-shift experiments and the increase of the pH during 'reverse'-shift experiments. The estimated parameters are used to compute the changing pH level in the models of the pH.induced metabolic shift in continuous cultures under phosphate limitation of C. acetobutylicum. Furthermore, the parameters can be applied to join different independent experiments into a single data set.

To fit the changing pH level, an exponential function and a ...

This presentation reports about the results from an investigation of a ClosTron-mutant lacking CoA-transferase activity. Using our two-population model developed for the wild type of C. acetobutylicum, we analyse the changes in the formation of products caused by that mutation. In particular, we focus on the investigation of the acid re-assimilation after the initiation of the pH shift. Our comparison of experimental data and simulation unravels that an CoA-independent re-assimilation mechanism ...

The acetone-butanol-ethanol (ABE) fermentation of Clostridium acetobutylicum attracts new attention because it provides a potential alternative for the synthesis of value added chemicals to petroleum and other fossil reserves. This fermentative metabolic process comprises two distinct metabolic states that differ in their product spectrum. Growing on starch or sugars the predominant fermentation products are acetate and butyrate during acidogenesis (high pH). In contrast, C. acetobutylicum produces ...

This presentation given at the 5th International Beilstein Symposium presents the development of a model for the pH-induced shift in C. acetobutylicum. Starting from experimental information, the model construction and underlying assumptions are explained. Furthermore, the required additions to the metabolic and genetic network caused by the used experimentals setup are established.

The established metabolic and genetic model is compared to dynamic shift experiments starting at acidogenesis and ...

Presentation by Thomas Millat of a tool for automatized analysis of flow cytometry data. It allows characterisation of different growth modalities, statistical measures of mean and variance and estimation of population overlap all along with appropriate visualization.