Proteases are key molecules in biological systems. They modify numerous proteins by hydrolytic cleavage, thus controlling and executing many physiological processes. Their intricate networks require a tight regulation to prevent fortuitous proteolysis. Where this regulation fails, proteases trigger pathologies such as neurodegeneration, inflammation, and cancer. Many therapeutic approaches are directed towards proteases or their natural inhibitors, already leading to drugs against life threatening diseases. The tight regulation of proteases by posttranslational modifications makes current functional genomics technologies unsuitable to fully establish biological relevance. CAMP will lay the groundwork to study and understand proteases through activity labeling and functional imaging in cells. Specifically, we will investigate the substrate specificity of proteases using large peptide libraries, derive fluorescent labeling molecules from the sequence information gathered, and use these molecules to investigate proteolytic activities in cellular environments. A set of 45 proteases covering four prototypic protease subfamilies has been selected taking into account scientific relevance, structural diversity, and potential socio-economic interest. Given the estimated number of 600 to 1100 proteases in the human genome, our selected set constitutes a significant representation and will establish the feasibility of our approach to address the protease proteome.CAMP's proteases will serve as prototypes to develop novel protease-specific technologies and probes for studying expression and folding, the activity state of proteases and their endogenous interaction partners in vitro and in vivo. The gathered information will be annotated in a public repository. We expect that the derived insights will foster high-throughput approaches and research, leading to new avenues in drug discovery using integrated data on the protease proteome.
|Effective start/end date||1/01/06 → 30/06/09|
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