The genome sequences of microbial organisms responsible for diseases of world-wide medical importance have been sequenced or will be available in the near future. Technologies for producing large numbers of proteins have been developed and high-throughput assays such as protein micro arrays have been clinically validated for detecting the presence of antibodies, in serum, directed against microbial antigens. These achievements offer the opportunity of investigating the natural immune response against the w hole proteome of a variety of micro-organisms. Powerful combinations of genomic information, molecular tools and immunological assays are becoming available to help identify the antigens that function as targets of protective immunity or could be used as m arkers for serodiagnosis. We propose here to identify in micro-organisms of great medical relevance (M. pneumoniae, C. pneumoniae, L. pneumophila, coronavirus spp and P. falciparum), a large collection of surface and secreted proteins as well as putative e ndotoxins. This protein repertoire will be produced as recombinant molecules or as sets of overlapping synthetic peptides and printed on array slides. The serum reactivity of groups of individuals with proven historyof exposure to the selected micro-organi sms will be analysed against the arrayed proteins to identify diagnostic markers and correlates of protection. This project will significantly expand the SMEs bank of Intellectual Property and contribute to expertise within the RTDs. It is anticipated tha t the proposed work in high throughput protein expression, software analysis, surface peptides synthesis, protein and peptide surface capture, and array reader instrumentation will create an integrated platform of great commercial and research value. Fina lly it will contribute to unravelling how the humoral immune response interacts with the microbial proteomes thus filling the gap between genomic data and development of novel vaccines and diagnostic tools.