Descrizione del progetto
Svelare i misteri dell’invecchiamento
Esistono molte teorie sui meccanismi alla base dell’invecchiamento cellulare che implicano danni al DNA e danni ossidativi per le proteine. Tuttavia, l’eziologia precisa rimane poco compresa. Lo scopo del progetto CarboPore, finanziato dall’UE, è quello di studiare il contributo delle proteine danneggiate dall’ossidazione all’invecchiamento cellulare. I ricercatori lavoreranno sull’ipotesi che aggregati proteici associati all’età possano causare danni e permeabilità della membrana. A tal fine, valuteranno l’impatto degli aggregati proteici sull’integrità della membrana cellulare utilizzando tecniche avanzate di imaging e biochimiche. I risultati del progetto sveleranno nuovi aspetti cellulari e molecolari dell’invecchiamento, facendo luce su questo complesso processo.
Obiettivo
Aging is one of the greatest mysteries in biology and a considerable contemporary societal challenge. Despite extensive research, the etiology of aging remains poorly understood. Most current theories focus on DNA damage as the root cause of aging. However, this view has been challenged by discovery that oxidative damage to proteins alone is sufficient to recapitulate molecular and cellular hallmarks of aging. In this project, we aim to elucidate the mechanism through which oxidatively damaged/carbonylated proteins lead to age-associated cellular dysfunction. Since misfolded, oxidatively damaged proteins form aggregates, and protein aggregates contribute to aging of various tissues, as well as lead to damage of cellular membranes, we hypothesize that age-associated increase in oxidative damage to proteins binding of the resulting protein aggregates to cellular membranes lead to membrane damage and permeabilization. To test this hypothesis, we will characterize oxidatively damaged oligomers and aggregates and assess their association with cellular membranes. Membrane damage will be evaluated upon its exposure to oxidized oligomers in vitro, using artificial lipid vesicles, and in living bacterial and mammalian cells. Interdisciplinary approaches will be used, including advanced imaging techniques such as atomic force microscopy, stimulated emission depletion microscopy and Fourier transform infrared microscopy and spectroscopy, mass spectrometry and various biochemical techniques. During the fellowship, the applicant will acquire skills necessary for reaching a leading independent position, basic entrepreneurial experience and will be given an opportunity to promptly commercialize her research. Moreover, the fellowship will lead to creation of several new sustainable international networks.
Campo scientifico
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- natural sciencesphysical sciencesopticsmicroscopy
- natural sciencesbiological sciencesbiochemistrybiomoleculeslipids
- natural scienceschemical sciencesanalytical chemistrymass spectrometry
- natural sciencesphysical sciencesopticsspectroscopy
Parole chiave
Programma(i)
Argomento(i)
Meccanismo di finanziamento
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinatore
21000 Split
Croazia