The deciphering of the human genome laid the ground for a far more challenging task: the understanding of the intricate and diverse mode of action of the gene products, the proteins. The relative lack of appropriate technologies capable to deal with this c omplexity, makes the functional, molecular deconvolution of the proteome a still distant scientific goal of prime importance. Our research will develop and use novel enzyme microarray technologies (EMTs), a uniquely powerful tool for activity-based proteom ics. This technology relies, among other novelties, on the development of a variety of chemical probes that will monitor the activity of a multitude of microarrayed enzymes. We will use the enzyme microarray technology in our laboratory in conjunction with designed chemical libraries in order to perform a detailed, en masse, molecular understanding of the activity of important families of enzymes such as proteases, enzymes involved in phosphorylation/dephosphorylation, as well as of enzymes involved in the ubiquitination pathway. Large scale specificity correlations between the substrate specificity profiles of enzymes from these families will substantiate new hypothesis about the involvment of important enzymes in networks that govern many important biochem ical processes. The versatility and reliability of this technology can be used in two practically relevant formats: High-Throughput Screening and activity-based diagnostics. Our research is directly relevant to the Thematic Priority 1 of FP6 and will be ac hieved through the creation of a team involving the international mobility of the team members.
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