Analysis of global control of Escherichia coli carbohydrate uptake

<p>Abstract</p> <p>Background</p> <p>Global control influences the regulation of many individual subsystems by superimposed regulator proteins. A prominent example is the control of carbohydrate uptake systems by the transcription factor Crp in <it>Escherichia coli</it>. A detailed understanding of the coordination of the control of individual transporters offers possibilities to explore the potential of microorganisms e.g. in biotechnology.</p> <p>Results</p> <p>An o.d.e. based mathematical model is presented that maps a physiological parameter – the specific growth rate – to the sensor of the signal transduction unit, here a component of the bacterial phosphotransferase system (PTS), namely EIIA^<it>Crr</it>. The model describes the relation between the growth rate and the degree of phosphorylation of EIIA ^{<it>crr </it>}for a number of carbohydrates by a distinctive response curve, that differentiates between PTS transported carbohydrates and non-PTS carbohydrates. With only a small number of kinetic parameters, the model is able to describe a broad range of experimental steady-state and dynamical conditions.</p> <p>Conclusion</p> <p>The steady-state characteristic presented shows a relationship between the growth rate and the output of the sensor system PTS. The glycolytic flux that is measured by this sensor is a good indicator to represent the nutritional status of the cell.</p

Modeling the electron transport chain of purple non-sulfur bacteria

Purple non-sulfur bacteria (Rhodospirillaceae) have been extensively employed for studying principles of photosynthetic and respiratory electron transport phosphorylation and for investigating the regulation of gene expression in response to redox signals. Here, we use mathematical modeling to evaluate the steady-state behavior of the electron transport chain (ETC) in these bacteria under different environmental conditions. Elementary-modes analysis of a stoichiometric ETC model reveals nine operational modes. Most of them represent well-known functional states, however, two modes constitute reverse electron flow under respiratory conditions, which has been barely considered so far. We further present and analyze a kinetic model of the ETC in which rate laws of electron transfer steps are based on redox potential differences. Our model reproduces well-known phenomena of respiratory and photosynthetic operation of the ETC and also provides non-intuitive predictions. As one key result, model simulations demonstrate a stronger reduction of ubiquinone when switching from high-light to low-light conditions. This result is parameter insensitive and supports the hypothesis that the redox state of ubiquinone is a suitable signal for controlling photosynthetic gene expression

Chemical process control : present status and future needs ; the view from European industry

Not only in Europe, chemical process control is characterized by a broad invasion of distributed control systems into chemical plants. The information integration from process control up to business management is a great challenge of today which follows from the overall computerization of production. Most of the recent progress in process automation results from the application of computer science paradigms to control systems, and of advanced developments in field instrumentation. Despite these advances and the considerable progress made in process control theory, there is only limited acceptance and application of modern advanced process control methodologies in industrial practice. This paper is an attempt to summarize the European discussion on the reasons for these facts

Logical network of genotoxic stress-induced NF-κB signal transduction predicts putative target structures for therapeutic intervention strategies

Genotoxic stress is induced by a broad range of DNA-damaging agents and could lead to a variety of human diseases including cancer. DNA damage is also therapeutically induced for cancer treatment with the aim to eliminate tumor cells. However, the effectiveness of radio- and chemotherapy is strongly hampered by tumor cell resistance. A major reason for radio- and chemotherapeutic resistances is the simultaneous activation of cell survival pathways resulting in the activation of the transcription factor nuclear factor-kappa B (NF-κB). Here, we present a Boolean network model of the NF-κB signal transduction induced by genotoxic stress in epithelial cells. For the representation and analysis of the model, we used the formalism of logical interaction hypergraphs. Model reconstruction was based on a careful meta-analysis of published data. By calculating minimal intervention sets, we identified p53-induced protein with a death domain (PIDD), receptor-interacting protein 1 (RIP1), and protein inhibitor of activated STAT y (PIASy) as putative therapeutic targets to abrogate NF-κB activation resulting in apoptosis. Targeting these structures therapeutically may potentiate the effectiveness of radio-and chemotherapy. Thus, the presented model allows a better understanding of the signal transduction in tumor cells and provides candidates as new therapeutic target structures

Visual setup of logical models of signaling and regulatory networks with ProMoT

BACKGROUND: The analysis of biochemical networks using a logical (Boolean) description is an important approach in Systems Biology. Recently, new methods have been proposed to analyze large signaling and regulatory networks using this formalism. Even though there is a large number of tools to set up models describing biological networks using a biochemical (kinetic) formalism, however, they do not support logical models. RESULTS: Herein we present a flexible framework for setting up large logical models in a visual manner with the software tool ProMoT. An easily extendible library, ProMoT's inherent modularity and object-oriented concept as well as adaptive visualization techniques provide a versatile environment. Both the graphical and the textual description of the logical model can be exported to different formats. CONCLUSION: New features of ProMoT facilitate an efficient set-up of large Boolean models of biochemical interaction networks. The modeling environment is flexible; it can easily be adapted to specific requirements, and new extensions can be introduced. ProMoT is freely available from

Nonlinear control of high purity distillation columns

Two simple models of distillation columns are studied to investigate their suitability for the practical use with exact I/O-linearization. An extension of exact I/O-linearization, the asymptotically exact I/O-linearization is applied to the control of a high purity distillation column, using one of these models to derive the static state feedback law. Simulation studies demonstrate the advantage of asymptotically exact I/O-linearization versus classical exact I/O-linearization techniques. Experimental results show the excellent performance of asymptotically exact I/O-linearization using a simple distillation model

Host-pathogen systems biology: logical modelling of hepatocyte growth factor and Helicobacter pylori induced c-Met signal transduction

<p>Abstract</p> <p>Background</p> <p>The hepatocyte growth factor (HGF) stimulates mitogenesis, motogenesis, and morphogenesis in a wide range of tissues, including epithelial cells, on binding to the receptor tyrosine kinase c-Met. Abnormal c-Met signalling contributes to tumour genesis, in particular to the development of invasive and metastatic phenotypes. The human microbial pathogen <it>Helicobacter pylori </it>can induce chronic gastritis, peptic ulceration and more rarely, gastric adenocarcinoma. The <it>H. pylori </it>effector protein cytotoxin associated gene A (CagA), which is translocated via a type IV secretion system (T4SS) into epithelial cells, intracellularly modulates the c-Met receptor and promotes cellular processes leading to cell scattering, which could contribute to the invasiveness of tumour cells. Using a logical modelling framework, the presented work aims at analysing the c-Met signal transduction network and how it is interfered by <it>H. pylori </it>infection, which might be of importance for tumour development.</p> <p>Results</p> <p>A logical model of HGF and <it>H. pylori </it>induced c-Met signal transduction is presented in this work. The formalism of logical interaction hypergraphs (LIH) was used to construct the network model. The molecular interactions included in the model were all assembled manually based on a careful meta-analysis of published experimental results. Our model reveals the differences and commonalities of the response of the network upon HGF and <it>H. pylori </it>induced c-Met signalling. As another important result, using the formalism of minimal intervention sets, phospholipase Cγ1 (PLCγ1) was identified as knockout target for repressing the activation of the extracellular signal regulated kinase 1/2 (ERK1/2), a signalling molecule directly linked to cell scattering in <it>H. pylori </it>infected cells. The model predicted only an effect on ERK1/2 for the <it>H. pylori </it>stimulus, but not for HGF treatment. This result could be confirmed experimentally in MDCK cells using a specific pharmacological inhibitor against PLCγ1. The <it>in silico </it>predictions for the knockout of two other network components were also verified experimentally.</p> <p>Conclusion</p> <p>This work represents one of the first approaches in the direction of host-pathogen systems biology aiming at deciphering signalling changes brought about by pathogenic bacteria. The suitability of our network model is demonstrated by an <it>in silico </it>prediction of a relevant target against pathogen infection.</p

SYSTEMORIENTIERTE BIOPROZESSTECHNIK: INTERDISZIPLINÄRE FORSCHUNG IN BIOLOGIE, SYSTEM- UND COMPUTERWISSENSCHAFTEN

Die aktuelle Forschung in der molekularen Genetik und die Erfolge bei der Analyse von Genexpression und Proteinfunktion führen zu einer bisher unerreichten Fülle von Informationen über biologische Phänomene. Damit ergeben sich neben der medizinischen Anwendung auch neue Möglichkeiten und Aufgaben in der biotechnologischen Produktion von Wirkstoffen. Um dieses biologische Potenzial voll ausschöpfen zu können, bedarf es jedoch verstärkt interdisziplinärer Forschung in Biologie, System- und Computerwissenschaften. Der hier skizzierte Forschungsansatz soll langfristig zum Aufbau eines „Virtuellen Biologischen Labors“ führen, in dem Experimente am Rechner analog zu Experimenten im Labor durchgeführt werden können. Damit steht in Forschung und Lehre ein Werkzeug zur Vermittlung quantitativer und qualitativer Aspekte von zellulären Stoffwechsel- und Regulationsvorgängen zur Verfügung