EUGeneHeart will develop new approaches to prevent and treat heart failure through analysis of the genomics of signalling. Our strategy is based on the hypothesis that beneficial and maladaptive forms of hypertrophy exist and that heart failure is frequently preceded by maladaptive hypertrophy. We will dissect both adaptive and maladaptive signalling in hypertrophy to identify beneficial and maladaptive components of signal transduction in hypertrophy and heart failure. The EUGeneHeart consortium forms an extremely integrated project comprised of six major tasks. In Task 1, murine models will be analysed (phenotyped) in an integrated matrix approach: Wildtype mice will be subjected to pressure overload, myocardial infarction, and chronic exercise, genetically modified mice with a beneficial response to these stressors will be compared for differences in signal transduction. Task 2 identifies new players in different forms of hypertrophy and failure using screening techniques including proteomics and microarrays, forward and reverse genetics in drosophila and zebrafish, validation in murine models and patient cohorts. Task 3 exploits knowledge generated in the first two tasks and translates knowledge on existing pharmacological interventions to generate new candidate drugs in close involvement of SME's. Candidate small molecules and molecule libraries will be tested in a successive developmental platform. This will lead to patent filing, licensing strategies and to phase I and II clinical trials. Task 4 contains specific questions related to sex differences and to signalling in hypertrophy. Our approach takes account of national research activities and recruits knowledge, patients and tissues at a European level.Task 5 includes a training initiative and Task 6 contains the Management activities of the project. The ultimate accomplishment will include improvement of health, reduction of health expenses,creation of new jobs and economic benefit.