Project description DEENESFRITPL New targets for age-related diseases Senescence is a cellular mechanism associated with an irreversible proliferative arrest. This process contributes to age-related tissue dysfunction and diseases such as those characterised by neurodegeneration. Funded by the Marie Skłodowska-Curie Actions programme, the MitoSen project aims to elucidate key mechanisms responsible for cellular senescence with a goal to eliminate senescent cells from patients. The project focuses on mitochondria as key players in the process and on Cyclophilin D protein known for its role in regulating the permeability of the mitochondrial membrane. Project findings will determine the implication of Cyclophilin D in senescence as well as the outcome of its modulation. Show the project objective Hide the project objective Objective Ageing-related diseases are tightly correlated with the accumulation of senescent cells. While the selective elimination of senescent cells is a primary therapeutical goal in the field, no clinically approved treatment currently exists, which constitutes an important research gap. Abundant evidence highlights how changes in mitochondria and cellular metabolism can be both cause and consequence of the senescent phenotype and suggests a possible role of this organelle in the specific targeting of these cells. Through a CRISPR/Cas9-based screening, Serrano’s laboratory identified Cyclophilin D (CypD) as a promising candidate target, since its inactivation leads to the selective elimination of senescent cells while being non-toxic for control proliferating cells. CypD is a matrix isomerase involved in various mitochondrial functions, including the regulation of cell death and the opening of the mitochondrial permeability transition pore, a non-specific pore in the inner mitochondrial membrane, by sensitising it to calcium and reactive oxygen species. Interestingly, additional functions have been described for CypD, including proteins scaffolding, as it binds to several mitochondrial proteins, apoptosis and mitophagy control, and regulation of the electron transport chain activity. This project will study CypD as a novel, non-invasive senolytic target and provide a molecular understanding of its modulation in senescence biology, taking advantage of the various well-established senescence models developed in Serrano’s laboratory, including human and mouse cells and in vivo models. The ultimate goal is to improve the therapeutic outcome of senescence-associated diseases by developing new strategies for the detection and elimination of senescent cells in patients. Fields of science natural scienceschemical sciencesinorganic chemistryalkaline earth metalsnatural sciencesbiological sciencesbiochemistrybiomoleculesproteins Programme(s) HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme Topic(s) HORIZON-MSCA-2021-PF-01-01 - MSCA Postdoctoral Fellowships 2021 Call for proposal HORIZON-MSCA-2021-PF-01 See other projects for this call Funding Scheme HORIZON-AG-UN - HORIZON Unit Grant Coordinator FUNDACIO INSTITUT DE RECERCA BIOMEDICA (IRB BARCELONA) Net EU contribution € 165 312,96 Address CARRER BALDIRI REIXAC 10-12 PARC SCIENTIFIC DE BARCELONA 08028 Barcelona Spain See on map Region Este Cataluña Barcelona 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 No data
