Research Groups > Quantitative Systems Biology

The main goal of the the Quantitative Systems Biology group is to carry out an interdisciplinary research programme aimed at predicting disease phenotypes that occur whenever the genetic regulatory apparatus of signaling pathways and transcriptional networks is defective. As a consequence, we will be able to make use of the quantitative understanding of the dynamics of specific biological networks and associated diseases to provide a rigorous strategy leading to novel, multi-target and more personalized therapeutics.

Our studies are focussed towards the Calcineurin/NFAT signal transduction pathway, an important vertebrate pathway. It is activated by various ligand-receptor combinations in different tissues, thereby controlling organogenesis, and is centered around the family of NFAT transcription factors. The pathway has been implicated in a wide variety of human diseases, ranging from immune system failure to osteoporosis to heart valve defects and mental retardation and recently to Down Syndrome.

The NFAT circuit with a minimal set of kinetic constanst indicated. Important features are positive feedback (green arrows) negative feedback (red) and parallel, signal integrating pathways (yellow)

More specifically, we are interested in experimentally measuring and quantifying all the necessary kinetic parameters and the absolute mRNA and protein concentrations of the constituents of the Calcineurin/NFAT signaling pathway in a variety of tissues. In addition, we use mathematical modelling to simulate and accurately predict the associated spatio-temporal dynamics and discover new pathway modulators. By means of computational predictions and experimental verification of the combinatorial logic, tissue specificity and DNA binding properties of NFAT trancription complexes, we seek to extend the circuit above and to simulate its in vivo dynamic properties.