Objectif The objectives of the present project are to study cellular and molecular mechanisms of leukotriene biosynthesis. The work is divided into two major sections, i.e. 1. Structure and function of enzymes in leukotriene biosynthesis, and 2. Cellular regulation of enzyme activities and gene expression. Consequently, it will address the issues of activation, maintenance and regulation of the cascade with the ultimate goal to understand and gain control of the biosynthetic machinery.Leukotrienes, a family of paracrine hormones within the arachidonic acid cascade, are regarded as powerful chemical mediators of allergic and inflammatory reactions. Several lines of evidence point to a crucial role of leukotrienes in the pathophysiology of respiratory problems and asthma. Hence, to control the biosynthesis and actions of leukotrienes is one important therapeutic strategy in the treatment of asthma and related inflammatory and allergic diseases. An important effort will be made to characterize, at a molecular level, central enzymes and other cellular factors involved in leukotriene biosynthesis. This work includes enzyme purification and characterization, molecular cloning of both cDNAs and genomic sequences, gene promoter characterization, expression of recombinant enzymes, and site-directed mutagenesis. Detailed information on functional elements and catalytic mechanisms of individual enzymes is expected to be instrumental for the design of more potent and specific enzyme inhibitors, which can be developed into novel anti-asthmatic drugs. Using cellular models of leukotriene biosynthesis, expression of enzyme activity, protein and mRNA will be studied and the potential effects of post-translational modification of enzymes, cytokines, degree of cellular differentiation/maturation and cell-cell interactions. In particular, factors which determine gene transcription will be identified and characterized at a molecular level. A thorough understanding of regulatory mechanisms involved in cellular leukotriene biosynthesis, including factors of pathophysiological significance as well as novel potential targets for pharmacological intervention. Champ scientifique medical and health sciencesclinical medicinepneumologyasthmamedical and health sciencesbasic medicinephysiologypathophysiologynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes Programme(s) FP4-BIOMED 2 - Specific research, technological development and demonstration programme in the field of biomedicine and health, 1994-1998 Thème(s) 4.4.3 - Respiratory problems and asthma Appel à propositions Data not available Régime de financement CSC - Cost-sharing contracts Coordinateur KAROLINSKA INSTITUTE Contribution de l’UE Aucune donnée Adresse 9,Doktorsringen 9 A 171 77 STOCKHOLM Suède Voir sur la carte Coût total Aucune donnée Participants (4) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire JOHANN WOLFGANG GOETHE UNIVERSITAET FRANKFURT Allemagne Contribution de l’UE Aucune donnée Adresse 9,Marie-Curie-Strasse 9 60439 FRANKFURT AM-MAIN Voir sur la carte Coût total Aucune donnée Ruprecht-Karls-Universität Heidelberg Allemagne Contribution de l’UE Aucune donnée Adresse 58,Bergheimerstrasse 69115 Heidelberg Voir sur la carte Coût total Aucune donnée Università degli Studi di Bari Italie Contribution de l’UE Aucune donnée Adresse Piazza Giulio Cesare 70124 Bari Voir sur la carte Coût total Aucune donnée Århus Universitet Danemark Contribution de l’UE Aucune donnée Adresse 11,P.P. Oerumsgade 8000 Århus C Voir sur la carte Coût total Aucune donnée
