The proposed projects will exploit state of the art approaches to the identification of novel proteins important in Asthma and Rheumatoid arthritis. One fellow will focus on increasing our understanding of genes which are differentially expressed in disease tissue but which have little or no functional annotation. The role of these genes will be studied using detailed expression profiling in biopsies and primary cells from patients, as well as cell lines and samples from animal models of disease. Function will be studied by over expression and knockout studies, as well as antisense, antibody approaches. The second research fellow will pursue an approach combining unique in house structural knowledge with a prateomics strategy to increase our of the molecular interactions involved in regulation of the glucocorticoid receptor. Glucocorticoids are widely recognized as the most effective anti-inflammatory agents, however their cellular and molecular modes of action are still far from being fully elucidated. The proteomics strategy, combined with a cell based approach using functional readouts will lead to novel and therapeutically relevant insights into the treatment of inflammatory disease.