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Ergebnisse nach Hochschule und Institut
Publikation Coexistence in the chemostat as a result of metabolic by-products(Springer, 2006) Rausenberger, Julia; Schmidt, Julia K.; Reichl, Udo; Flockerzi, DietrichClassical chemostat models assume that competition is purely exploitative and mediated via a common, limiting and single resource. However, in laboratory experiments with pathogens related to the genetic disease Cystic Fibrosis, species specific properties of production, inhibition and consumption of a metabolic by-product, acetate, were found. These assumptions were implemented into a mathematical chemostat model which consists of four nonlinear ordinary differential equations describing two species competing for one limiting nutrient in an open system. We derive classical chemostat results and find that our basic model supports the competitive exclusion principle, the bistability of the system as well as stable coexistence. The analytical results are illustrated by numerical simulations performed with experimentally measured parameter values. As a variant of our basic model, mimicking testing of antibiotics for therapeutic treatments in mixed cultures instead of pure ones, we consider the introduction of a lethal inhibitor, which cannot be eliminated by one of the species and is selective for the stronger competitor. We discuss our theoretical results in relation to our experimental model system and find that simulations coincide with the qualitative behavior of the experimental result in the case where the metabolic by-product serves as a second carbon source for one of the species, but not the producer.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Signatures of gene expression noise in cellular systems(Elsevier, 2009) Rausenberger, Julia; Fleck, Christian; Timmer, Jens; Kollmann, MarkusNoise in gene expression, either due to inherent stochasticity or to varying inter- and intracellular environment, can generate significant cell-to-cell variability of protein levels in clonal populations. To quantify the different sources of gene expression noise, several theoretical studies have been performed using either a quasi-stationary approximation for the emerging master equation or employing a time-dependent description, when cell division is taken explicitly into account. Here, we give an overview of the different origins of gene expression noise which were found experimentally and introduce the basic stochastic modeling approaches. We extend, and apply a time-dependent description of gene expression noise to experimental data. The analysis shows that the induction level of the transcription factor can be employed to discriminate the noise profiles and their characteristic signatures. On the basis of experimentally measured cell distributions, our simulations suggest that transcription factor binding and promoter activation can be modeled independently of each other with sufficient accuracy.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Photoconversion and nuclear trafficking cycles determine phytochrome A's response profile to far-red light(Cell Press, 02.09.2011) Rausenberger, Julia; Tscheuschler, Anke; Nordmeier, Wiebke; Wüst, Florian; Timmer, Jens; Schäfer, Eberhard; Fleck, Christian; Hiltbrunner, AndreasPhytochrome A (phyA) is the only photoreceptor in plants, initiating responses in far-red light and, as such, essential for survival in canopy shade. Although the absorption and the ratio of active versus total phyA are maximal in red light, far-red light is the most efficient trigger of phyA-dependent responses. Using a joint experimental-theoretical approach, we unravel the mechanism underlying this shift of the phyA action peak from red to far-red light and show that it relies on specific molecular interactions rather than on intrinsic changes to phyA's spectral properties. According to our model, the dissociation rate of the phyA-FHY1/FHL nuclear import complex is a principle determinant of the phyA action peak. The findings suggest how higher plants acquired the ability to sense far-red light from an ancestral photoreceptor tuned to respond to red light.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Quantifying origins of cell-to-cell variations in gene expression(Cell Press, 15.11.2008) Rausenberger, Julia; Kollmann, MarkusA general dynamic description of protein synthesis was employed to quantify different sources of gene expression noise in cellular systems. To test our approach, we use time-resolved expression data of individual human cells and, from this information, predict the stationary cell-to-cell variation in protein levels in a clonal population. For three of the four human genes investigated, the cellular variations in expression level are not due to fluctuations in promoter activity or transcript copy number, but are almost exclusively a consequence of long-term variations of gene regulatory factors or the global cellular state. Moreover, we show that a dynamic description is much more reliable to discriminate extrinsic and intrinsic sources of noise than it is on grounds of cell-cycle averaged descriptions. The excellent agreement between the theoretical predictions and the experimentally measured noise strengths shows that a quantitative description of gene expression noise is indeed possible on the basis of idealized stochastic processes.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation A novel concept combining experimental and mathematical analysis for the identification of unknown interspecies effects in a mixed culture(Wiley, 08/2011) Schmidt, Julia K.; Riedele, Christian; Regestein, Lars; Rausenberger, Julia; Reichl, UdoBacteria in natural habitats only occur in consortia together with various other species. Characterization of bacterial species, however, is normally done by laboratory testing of pure isolates. Any interactions that might appear during growth in mixed-culture are obviously missed by this approach. Existing experimental studies mainly focus on two-species mixed cultures with species specifically chosen for their known growth characteristics, and their anticipated interactions. Various theoretical mathematical studies dealing with mixed cultures and possible interspecies effects exist, but often models cannot be validated due to a lack of experimental data. Here, we present a concept for the identification of interspecies effects in mixed cultures with arbitrary and unknown single-species properties. Model structure and parameters were inferred from single-species experiments for the reproduction of mixed-culture experiments by simulation. A mixed culture consisting of the three-species Pseudomonas aeruginosa, Burkholderia cepacia, and Staphylococcus aureus served as a model system. For species-specific enumeration a quantitative terminal restriction length polymorphism (qT-RFLP) assay was used. Based on models fitted to single-species cultivations, the outcome of mixed-culture experiments was predicted. Deviations of simulation results and experimental findings were then used to design additional single-cell experiments, to modify the corresponding growth kinetics, and to update model parameters. Eventually, the resulting mixed-culture dynamics was predicted and compared again to experimental results. During this iterative cycle, it became evident that the observed coexistence of P. aeruginosa and B. cepacia in mixed-culture chemostat experiments cannot be explained on the basis of glucose as the only substrate. After extension of growth kinetics, that is, for use of amino acids as secondary substrates, mixed-culture simulations represented the experimental findings very well. According to the model structure, as motivated by single-species experiments, the growth of P. aeruginosa and B. cepacia on glucose and amino acids could be assumed to be independent of each other. In contrast, both substrates are taken up simultaneously by S. aureus.01A - Beitrag in wissenschaftlicher Zeitschrift