Pathways & Gene Networks: Innate immunity and barrier function

Coordinator:    Prof. Dr. Philip Rosenstiel
Institution: Uniklinik Schleswig Holstein, Campus Kiel - Institut für Klinische Molekularbiologie
Determining the quantitative biology of genetic variants in disease genes and their encoded proteins in the context of complex inflammatory disorders represents a major challenge for cell biological approaches. This project aims to molecularly dissect identified disease susceptibility loci in order to understand the complex interplay of variants in the framework and signal transduction of each individual gene element. A special emphasis of this project will be cell biological follow-up of GWAS regions that are difficult to interprete on the genetic level, but have clear and replicated association signals.
The read-outs and functional assays will mainly address the molecular pathophysiology of inflammatory processes at epithelial interfaces. It aims at a quantitative integrated map of novel and known pathways, such as NOD-like receptors and autophagy
The overall aims are:
•    To understand quantitative biological effects of disease-associated sequence variants in a context of epithelial barrier function and innate immunity
•    To systematically analyze the genotype-dependent gene expression profile by using the network´s unique tissue bank and a large typable lymphoblast collection (n>300)
•    To describe the direct molecular framework, in which the proteins encoded by disease genes exert their cellular function
•    Employ genome-wide siRNA studies to delineate the functional network of the genes and their crosstalk with other genes in pathways relevant for adaptive immune responses
•    To unveil novel putative targets within these molecular frameworks feeding into other projects developing new diagnostics, therapy and, ultimately, preventive strategies
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