System Biology

Helmholtz Alliance System Biology (Helmholtz Alliance)

System biology combines classical experimental approaches and bioinformatics strategies to gain a comprehensive understanding of complex biological processes. The aim is to derive a simplified but general description of these mechanisms, which can lead to the identification of new regulatory cellular principles.

Within the “Helmholtz Alliance on System Biology“ our project “From pollutant molecule to cell fate: development of a model for system quantification and prediction” focuses on the signal transduction pathway of the arylhydrocarbon receptor (AhR). This cytosolic transcription factor is particularly important in environmental research, since AhR can be activated by multiple environmental pollutants (e.g. TCDD, PCBs, PAHs). Describing the subsequent complex cellular response upon AhR activation is a central part of our project. Our aim is to derive a time- and space-independent model of AhR signal transduction. Starting with the entry of the pollutant into the cell and following the cellular response on the gene and protein level. For this project we use an in vitro model of murine liver cells, in which we investigate the effects of the model pollutant benzo(a)pyrene (common PAH). Our derived results and mathematical models can be of great value for environmental pollutant assessment in the future since they can be generalized and transferred to other in-vitro-systems or applied to other chemicals.

There are a manifold of experimental approaches, which can be used for mathematical modeling. We focus on receptor DNA interactions (chromatin immunoprezipitation, ChIP) and the concomitant transcriptional and/or phenotypic cellular response. A direct correlation of the receptor activation can be visualized by high-throughput-measurements of receptor translocation (fluorescence-microscopy, BD Pathway™ 855). This interdisciplinary project is a cooperation of several experimentally working groups with bioinformaticians as well as modelers.