My main area of research is the mathematical modeling and analysis of signal transduction pathways in mammalian cells. Broadly speaking, I am interested in the application of engineering methods to understanding signaling processes [3].
In particular, I apply an engineering-inspired modular approach to decompose signaling networks and facilitate their analysis [9,10,11]. Accordingly, to set up models I use ProMoT, a modeling tool which allows to create models in a modular manner.
The formalism I use mostly is kinetic modeling (typically ordinary differential equations). Here, key issues while dealing with experimental data are parameter estimation and model discrimination. A related question is model falsification: given a set of data, exclude those models which can by no means reproduce that data. We are collaborating with the Systems and Control Theory Group here at the Max-Planck-Institute on the development of methods for discarding network structures. We have shown that Feinberg's Chemical Reaction Network Theory can be a useful tool for that purpose [8,1,12,14].
Another important issue I am involved with is the reduction of models of signaling networks [10,13]. In particular, we are concentrating on the reduction of the combinatorial complexity which arises in signaling networks [7].
Besides the kinetic approach, I also apply qualitative and structural approaches, based on a logical formalism, to the analysis of signaling networks [6]. To support the set-up process, we have extended the abilities of ProMoT to model large signaling networks using a boolean formalism [4]. The models can be exported, among others formats, to CellNetAnalyzer, a toolbox which allows to analyze the structural properties of signaling networks in a visual manner [5].
As case study for the different methods we are developing, we use mainly the signaling processes in T-cells, in collaboration with the Institute of Immunology at the University of Magdeburg. For the dynamical approach, we focus on the T-cell Receptor (TCR)-induced MAP Kinase Cascade, while for structural analysis we have analyzed a large network comprising the main signaling events downstream of the TCR [2].
I am also interested in other signaling systems such as receptor tyrosine kinases (in particular, the EGF induced MAPK Cascade) and TGF-beta signaling. A key question we try to tackle in our group is the crosstalk among different pathways, particularly among pro- and antiapoptotic signaling pathways and their connection the cell cycle.