Proteòmica funcional i estructural integrades: aproximacions analítiques i aplicacions a proteases i inhibidors

The proposed research Project involves an integrated development of both experimental and bioinformatics tools for proteomics and genomics, aimed to the massive identification and characterization of certain protein species and their specific interaction with other proteins and actual or synthetic (combinatorial) ligands. The application of the results to natural protein systems of biotechnological interest and inherent complexity will also be a prime mover of the project. On some protein targets, either previously selected or identified by the use of high-throughput methodologies, structural functional and chemogenomic strategies will be applied. Proteases and their protein inhibitors will be preferably used as models, given the expertise that our group has accumulated over the years with those proteins, and also because the challenge imposed by their great ease of autolysis and their destructive capacity on interacting proteins. Methods and strategies will be developed to cope with these issues both in their production/functional detection and profound structural analysis. In this latter case, we shall focus on protease-inhibitor complexes, both recombinant wild-type and modified protein forms will be studied. Natural, redesigned or synthetic ligands will be searched to facilitate the analysis and to control the target proteins. These which will be selected based on their potential pharmacological applicability because of their involvement I processes ob biotechnological, biomedical or social interest such as malaria, amebiasis, cancer, fibrinólisis, amiloidosis or the generation of new biomaterials