Systems Biology of Sepsis
Our aim is to develop systems biology models to
- spot molecular players and pathways relevant for the unbound inflammatory response in order to
- decipher molecular mechanisms leading to
- the identification of biomarkers for early diagnosis, and to
- the identification of specific targets for therapy.
For this, we will develop new methods and integrate omics datasets of septic patients’ blood and of several tissues of animal models, such as gene expression profiles, but also genomics, metabolomics, proteomics data and next generation sequencing data. We will develop models to observe regulation of cellular signaling and metabolism, also within different organs. We will analyze the impact of genetic variants on the clinical course of sepsis patients. In particular, loss-of-function gene variants will be associated with unexpectedly good disease progression, which will lead to potential drug targets for therapy. Methodologically, we will develop gene regulatory models for signaling, regulation, and metabolism and interconnect them to understand the pathologic regulation of central pathways linking receptors, the mediating signaling pathways and in particular regulation of metabolism of the affected cells. In addition, we will set up dependency models, linking the regulation of the involved organs, to find crucial players mediating these signals. These players will serve for improved drug target predictions. The predictions of our models will be the basis for experimental validation and follow-up of CSCC cooperation partners.