Chronic inflammation is a prototypic systemic disorder resulting from the dysregulation of multiple, mechanistically unrelated higher order biological processes. In chronic inflammatory diseases a variety of "inputs" effect the recruitment and activation of immune and inflammatory cells to the site of lesions, thereby amplifying and perpetuating the inflammatory state. The underlying idea of this four-year proposal is that the most effective strategy to overcome barriers to progress in chronic inflammation is to promote the synergistic interaction of scientists from many disciplines to challenge the aforementioned processes using a reductionist approach. Based on the above assumptions, this Consotium has gathered 13 research Institutes, 2 SME, 48 research groups, 186 researchers and 91 student 13 research institutes with outstanding records or promise of research accomplishments, to focus this proposal on achieving a thorough understanding of a key basic process in chronic inflammation, namely directed inflammatory cell migration towards and across injured tissues. To achieve its scientific goals, the MAIN Consortium will be based on four developmental Research Programs (Tool Development Program, Target Identification Program, Target Validation Program and Drug Development Program), three Support Facilities (Imaging, Proteomics and Microarrays) and one Core Facility (Bioinformatics). The Programs comprising the scientific core are tightly interconnected and conceived as a logical sequence of highly integrated activities, each centered on a unifying objective and relatively homogeneous tasks. The Tool Development Program (TDP) will develop state of the art technological tools that are instrumental to make decisive scientific advancements in the field of cell migration. The Target Identification Program (TIP) will promote the identification and characterization of signaling pathways and/or molecular networks involved in defined aspects of inflammatory cell migration. In the Target Validation Program (TVP), targets identified in the TIP will be validated by testing them across cellular models, healthy and diseased animal models, different inducing stimuli and manipulating conditions. The TVP aims at combining the products of the TDP and the TIP to provide a unified explanation on how multiple "inputs" received by inflammatory cells result in spatially and temporally coordinated "outputs", as it pertains to cell migration and related biological processes occurring in chronically inflamed tissues. The Drug Development Program (DDP) will focus on selected target pathways/networks emerging from the TVP and will transfer them into a pipeline of drug development, using the premises of the biotechnological and pharmaceutical SMEs participating in this network. The three Support Facilities (Imaging, Microarrays and Proteomics) and the Bioinformatics Core will provide critical technological support for the efforts of the developmental research programs. To spread excellence through education and training both within and outside the Consortium's boundaries, MAIN will implement a Training and Education Program (TEP). The MAIN Consortium will use its existing infrastructures, the network of scientific institutes, Universities, and industries to organize practical courses and workshops for graduate students and technicians.