Description du projet
Dévoiler les mystères du vieillissement
Il existe de nombreuses théories sur les mécanismes qui sous‑tendent le vieillissement cellulaire impliquant l’ADN et les dommages oxydatifs des protéines. Toutefois, l’étiologie précise de ce processus reste encore mal comprise. L’objectif du projet CarboPore, financé par l’UE, consiste à étudier la contribution des protéines atteintes de dommages oxydatifs au vieillissement cellulaire. Des chercheurs partiront de l’hypothèse selon laquelle les agrégats protéiques associés à l’âge provoquent la perméabilisation et une lésion de la membrane. À cette fin, ils détermineront les répercussions des agrégats protéiques sur l’intégrité de la membrane cellulaire en utilisant des techniques avancées de biochimie et d’imagerie. Les résultats du projet dévoileront de nouveaux aspects moléculaires et cellulaires du vieillissement, faisant ainsi la lumière sur ce processus complexe.
Objectif
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.
Champ scientifique
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- natural sciencesphysical sciencesopticsmicroscopy
- natural sciencesbiological sciencesbiochemistrybiomoleculeslipids
- natural scienceschemical sciencesanalytical chemistrymass spectrometry
- natural sciencesphysical sciencesopticsspectroscopy
Mots‑clés
Programme(s)
Régime de financement
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinateur
21000 Split
Croatie