Asthma affects up to 30 million children and adults in Europe and many more around the world. Today, asthma can be treated but not cured. Major efforts to understand the mechanisms leading to the disease are needed to better intervene and potentially prevent asthma.Genetic susceptibility and environmental factors are thought to cause the disease. However, until recently systematic approaches to identify major genetic susceptibility factors were not feasible. Within the GABRIEL Consortium we lately identified a novel and major susceptibility locus specifically for childhood asthma on chromosome 17q21 by genome wide association studies. ORDML3, a gene in that locus seems to contribute significantly to the association with asthma. ORMDL3 is coding for a protein with so far unknown function located in the endoplasmic reticulum.With this project we aim to increase our understanding of ORMDL3 function and its role in asthma pathogenesis. Collaborating with the National Jewish Hospital in Denver, we will use transgenic mice to determine the biological profile of ORMDL3 in different cells and tissues and to identify interaction partners and pathways that involve ORMDL3. We will study the role of ORMDL3 in asthma genesis using asthma mouse models and explore the potential of ORMDL3 as a therapeutic target.This project will provide the opportunity to increase our knowledge on asthma considerably and at the same time, give the opportunity to acquire new research skills at the post doc level exactly as outlined by the aims of the “Marie Curie Outgoing Fellowship”. It will allow a substantial transfer of knowledge and establish close ties with one of the top 5 immunology centers in the US. Upon return from the US, the applicant will be integrated in a highly active and supportive research environment to establish herself as an independent researcher.