Development of high througput affinity protemics to search for drug targets in cancer.

Antibody array technology, mass-spectrometry and molecular biology techniques are combined to develop a new platform for screening of drug targets in cancer. The technology allows large-scale analysis of protein networks with high sample throughput. The p roject will develop large-scale analysis of protein networks that regulate cell division and turnover. Lund-Johansen (RH-Gaustad Institute of Immunology) has developed particle-based antibody arrays that combines high multiplexing (>1000) with high throug hput sample processing. The arrays are used to measure protein levels, post-translational modifications and protein-protein interactions in the cell cycle and apoptosis machineries and upstream kinase pathways. Disease-associated changes in proteins are d etected by cluster analysis and resolved further by mass spectrometry. Fleckenstein, who leads the RH-Gaustad FUGE node for mass spectrometry (MS) will use particle technology in novel protocols to enhance throughput and sensitivity MS. Aasheim, (Dept. o f Medical Genetics UUS) will apply knockdown strategies to measure effects of key molecules on biological parameters such as cell division and turnover. The project is integrated as a collaborative node in the Human Proteome Resource (HPR) and the EU pr ogram ProteomeBinders. The HPR is one of the largest functional genomics projects in Europe and currently establishing a comprehensive resource of antibodies for detection of the human proteome. Protein affinity arrays and affinity-based MS, have a wide range of applications in cell biology research and laboratory medicine. This project aims at developing high throughput affinity proteomics to a national platform.