Opis projektu
Zgłębianie tajników starzenia się
Istnieje wiele teorii na temat podstawowych mechanizmów starzenia się komórek, które powodują uszkodzenia DNA oraz uszkodzenia oksydacyjne białek, jednak ich dokładna etiologia pozostaje słabo poznana. Dlatego też celem finansowanego przez Unię Europejską projektu CarboPore jest zbadanie roli białek ulegających uszkodzeniu oksydacyjnemu w starzeniu się komórek. Punktem wyjścia dla badań będzie hipoteza, zgodnie z którą agregaty białkowe powiązane z wiekiem powodują uszkodzenia i permeabilizację błony. Uczeni ocenią wpływ agregatów białkowych na integralność błony komórkowej przy użyciu zaawansowanych technik obrazowania i technik biochemicznych. Projekt pozwoli na poznanie nowych komórkowych i molekularnych aspektów złożonych procesów starzenia.
Cel
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.
Dziedzina nauki
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- natural sciencesphysical sciencesopticsmicroscopy
- natural sciencesbiological sciencesbiochemistrybiomoleculeslipids
- natural scienceschemical sciencesanalytical chemistrymass spectrometry
- natural sciencesphysical sciencesopticsspectroscopy
Słowa kluczowe
Program(-y)
Temat(-y)
System finansowania
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Koordynator
21000 Split
Chorwacja