Biomedical research in the post genomic era will depend on the establishment of collaborative efforts between clinical and preclinical researchers, combining bedside medical research with experimental science. This project stems from initial gene expression studies on immune compromised patients with severe inflammatory disorders. The results allowed us to generate the hypothesis that reactive oxygen radicals are key anti-inflammatory agents in the immune system. We also embrace the novel idea that it is possible to stimulate an innate immune response without exciting harmful inflammation and moreover, that it is possible to identify molecular regulators as potential therapeutic targets that allow such an immune response. The proposed project will be multidisciplinary, incorporating old and new technologies in both the wet and dry lab environments that combine aspects of immunology, cell biology, bioinformatics and clinical microbiology. It will constitute the first comprehensive study of the role of oxygen radicals in inflammation and immunity outside the traditionally described roles of radicals in oxidative microbial killing and neutrophil apoptosis. In addition, it will highlight a novel set of immune regulators with therapeutic potential and provide a template for future biology-based drug discovery platforms that originate in the clinic.