Objective Heart failure has become a worldwide epidemic with more than 23 million people affected resulting in devastating consequences for patients and an enormous burden on health care systems. One in five heart failure patients dies within a year of diagnosis and survival estimates after diagnosis are 50% and 10% at 5 and 10 years, respectively. Despite intensive investigation, the molecular mechanisms leading to heart failure remain poorly understood. We will narrow this critical gap in knowledge by proposing a previously unattainable, comprehensive approach to define the genomic architecture and functional consequences of newly identified micropeptides from multiple classes of RNAs that previously were classified to be non-coding in cardiac biology and heart failure. Our approach is unique and novel in several ways. Thematically, our studies focus on novel classes of orphan peptides and their role in heart failure that have not been discovered previously. Our approach relies on innovative interdisciplinary efforts of scientists working in molecular genetics, genomics, computational biology, and cardiovascular research to identify and characterize pathophysiological pathways that converge on these novel peptides. We will identify these short peptides by using genome-wide measures of active translation and will harness unique clinical resources to ensure human relevance. Analysis of animal and cell models coupled with state-of-the-art biochemical and genetic tools will elucidate the function of newly identified micropeptides within the molecular and cellular pathways of cardiac biology and failure. Through these efforts we will discern fundamental causes of maladaptive responses in the heart and strategies to monitor and limit these. Fields of science natural sciencesbiological sciencesmolecular biologymolecular geneticsnatural sciencesbiological sciencesbiochemistrybiomoleculesnatural sciencesbiological sciencesgeneticsRNAmedical and health sciencesclinical medicinecardiology Keywords Cardiovascular genetics and genomics cardiovascular sciences heart heart failure gene expression long non-coding RNA circular RNA functional genomic Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-2017-ADG - ERC Advanced Grant Call for proposal ERC-2017-ADG See other projects for this call Funding Scheme ERC-ADG - Advanced Grant Host institution MAX DELBRUECK CENTRUM FUER MOLEKULARE MEDIZIN IN DER HELMHOLTZ-GEMEINSCHAFT (MDC) Net EU contribution € 2 319 514,00 Address ROBERT ROSSLE STRASSE 10 13125 Berlin Germany See on map Region Berlin Berlin Berlin Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 2 319 514,00 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all MAX DELBRUECK CENTRUM FUER MOLEKULARE MEDIZIN IN DER HELMHOLTZ-GEMEINSCHAFT (MDC) Germany Net EU contribution € 2 319 514,00 Address ROBERT ROSSLE STRASSE 10 13125 Berlin See on map Region Berlin Berlin Berlin Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 2 319 514,00
