Mathematical Modelling of TNF induced apoptosis and anti-apoptotic crosstalk in mammalian cells

Poster (2005)

Sensitivity Analysis of Escherichia coli's Tricarboxilic Acid Cycle under Anaerobic Conditions

in Proc. Foundations of Systems Biology in Engineering, FOSBE 2005 (2005)

Adaptive lambda-tracking for nonlinear higher relative degree systems

in Automatica (2005), 41(7), 1191-1200

This paper proposes a relatively simple adaptive controller for nonlinear systems with higher relative degree. The controller achieves lambda-tracking for a large class of nonlinear systems, i.e. it ... [more ▼]

This paper proposes a relatively simple adaptive controller for nonlinear systems with higher relative degree. The controller achieves lambda-tracking for a large class of nonlinear systems, i.e. it asymptotically stabilizes the system up to an error of at most lambda which is chosen by the user. Only little information on the system is needed in the sense that no model needs to be known for the controller design, but only structural information like the relative degree and a lower bound on the positive high-frequency gain. The zero-dynamics does not need to be asymptotically stable, boundedness is sufficient. The controller consists of a high-gain observer, a high-gain observer-state feedback and a common adaptation of both high-gain parameters. The adaptation increases the gains of the observer and the state-feedback whenever the control objective, namely that the tracking error is of magnitude not larger than lambda, is not attained. It is proved that the controller's adaptation converges and the control objective is achieved at least asymptotically. (c) 2005 Elsevier Ltd. All rights reserved. [less ▲]

Domain oriented model reduction of signal transduction models

Poster (2004, October)

Control Engineering in Systems Biology

Scientific conference (2004, July 08)

Systems Biology: A Systems Theory Perspective

Conference (2004, February)

Detailed Mathematical Modeling of Metabolic and Regulatory Networks

in BIOforum Europe (2004), 2004(2), 62--64

Bistability analyses of a caspase activation model for receptor-induced apoptosis

in Journal of Biological Chemistry (2004), 279(35), 36892-36897

Apoptosis is an important physiological process crucially involved in development and homeostasis of multicellular organisms. Although the major signaling pathways have been unraveled, a detailed ... [more ▼]

Apoptosis is an important physiological process crucially involved in development and homeostasis of multicellular organisms. Although the major signaling pathways have been unraveled, a detailed mechanistic understanding of the complex underlying network remains elusive. We have translated here the current knowledge of the molecular mechanisms of the death-receptor-activated caspase cascade into a mathematical model. A reduction down to the apoptotic core machinery enables the application of analytical mathematical methods to evaluate the system behavior within a wide range of parameters. Using parameter values from the literature, the model reveals an unstable status of survival indicating the need for further control. Based on recent publications we tested one additional regulatory mechanism at the level of initiator caspase activation and demonstrated that the resulting system displays desired characteristics such as bistability. In addition, the results from our model studies allowed us to reconcile the fast kinetics of caspase 3 activation observed at the single cell level with the much slower kinetics found at the level of a cell population. [less ▲]

Reduction of mathematical models of signal transduction networks: simulation-based approach applied to EGF receptor signalling

in IEE Proceedings - Systems Biology (2004), 1(1), 159-169

Biological systems and, in particular, cellular signal transduction pathways are characterised by their high complexity. Mathematical models describing these processes might be of great help to gain ... [more ▼]

Biological systems and, in particular, cellular signal transduction pathways are characterised by their high complexity. Mathematical models describing these processes might be of great help to gain qualitative and, most importantly, quantitative knowledge about such complex systems. However, a detailed mathematical description of these systems leads to nearly unmanageably large models, especially when combining models of different signalling pathways to study cross-talk phenomena. Therefore, simplification of models becomes very important. Different methods are available for model reduction of biological models. Importantly, most of the common model reduction methods cannot be applied to cellular signal transduction pathways. Using as an example the epidermal growth factor (EGF) signalling pathway, we discuss how quantitative methods like system analysis and simulation studies can help to suitably reduce models and additionally give new insights into the signal transmission and processing of the cell [less ▲]

Der Einsatz neuer Medien in der regelungstechnischen Ausbildung

Poster (2003)