Descrizione del progetto DEENESFRITPL Svelare i meccanismi dell’invecchiamento Con l’aumentare dell’aspettativa di vita, svelare i meccanismi dell’invecchiamento è fondamentale per fornire una vita di qualità alle persone con 65 anni e più. La perdita di integrità nucleare e i relativi difetti nella meccanica nucleare sono caratteristiche tipiche dell’invecchiamento. Nelle cellule dei mammiferi, le capacità strutturali del nucleo sono supportate dalla lamina nucleare, principalmente la lamina A (LA) e la relativa interazione con l’involucro nucleare. Il progetto LipLAge, finanziato dall’UE, esplorerà il modo in cui l’interazione tra la lamina A e i lipidi della membrana nucleare interna influenzano l’architettura della lamina nucleare e l’integrità strutturale nucleare durante l’invecchiamento naturale. Il progetto applicherà un approccio integrato di biofisica molecolare basato sui lipidi per studiare l’involucro nucleare durante l’invecchiamento umano sano. Mostra l’obiettivo del progetto Nascondi l’obiettivo del progetto Obiettivo Aging is a major risk factor for many human pathologies. At a time when we are living longer than ever before, untangling the mechanisms of this biological deterioration is absolutely critical if we aim at providing a better quality of life for aging individuals. The loss of nuclear integrity, and the consequent defects in nuclear mechanics, is already among widely considered hallmarks of aging. In mammalian cells, the structural properties of the nucleus are maintained by the nuclear lamina (NL), especially lamin A (LA), and its interaction with the nuclear envelope (NE). In this innovative project, our working hypothesis is built upon the observation that progerin – truncated form of LA prevalent in premature aging – is abnormally associated with the inner nuclear membrane (INM) and the LA, due to its permanent farnesylation. Moreover, progerin levels were also shown to increase in healthy aged individuals, suggesting that LA and progerin differences in membrane association might be intimately involved in healthy human aging. Hence, the main goal of this project is to understand how the interplay between LA (at different proteolytic stages) and INM lipids affects NL architecture and nuclear structural integrity during physiological aging. To address this question, we will tackle lamin-lipid interactions (and lamin polymerization) in membrane models mimicking the NE during healthy and premature aging, and in intact nuclei, using a set of quantitative techniques, including fluorescence-based methods, atomic force microscopy and lipidomics. Overall, this is the first time a comprehensive lipid-driven molecular biophysics approach will be applied to the NE during healthy human aging. By achieving the proposed objectives, we will provide new knowledge on the role of INM lipids in proper nuclear function and aging. Campo scientifico natural sciencesphysical sciencesopticsmicroscopynatural sciencesbiological sciencesbiochemistrybiomoleculeslipidsmedical and health sciencesbasic medicinepathologynatural sciencesbiological sciencesbiophysics Parole chiave Molecular biophysics Inner-nuclear membrane Nuclear structural integrity Lamin A polymerization Lamin-lipid interaction Human aging Fluorescence spectroscopy and microscopy AFM Lipidomics Programma(i) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Argomento(i) MSCA-IF-2019 - Individual Fellowships Invito a presentare proposte H2020-MSCA-IF-2019 Vedi altri progetti per questo bando Meccanismo di finanziamento MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF) Coordinatore INSTITUTO DE MEDICINA MOLECULAR JOAO LOBO ANTUNES Contribution nette de l'UE € 147 815,04 Indirizzo AVENIDA PROF EGAS MONIZ 1649 028 Lisboa Portogallo Mostra sulla mappa Regione Continente Área Metropolitana de Lisboa Área Metropolitana de Lisboa Tipo di attività Research Organisations Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 147 815,04
