Descripción del proyecto
Revelación de los misterios del envejecimiento
Existen muchas teorías sobre los mecanismos subyacentes al envejecimiento celular en los que intervienen los daños en el ADN y el daño oxidativo en las proteínas. Sin embargo, todavía no se comprende bien su etiología concreta. El objetivo del proyecto financiado con fondos europeos CarboPore es investigar la contribución de las proteínas dañadas por oxidación en el envejecimiento celular. Los investigadores del proyecto trabajarán con la hipótesis de que agregados de proteínas relacionados con la edad dañan las membranas y causan permeabilización. Para este fin, evaluarán el impacto de los agregados de proteínas sobre la integridad de la membrana celular mediante imagenología avanzada y técnicas bioquímicas. Los resultados del proyecto revelarán nuevos aspectos moleculares y celulares del envejecimiento y arrojarán luz sobre este proceso complejo.
Objetivo
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.
Ámbito científico
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- natural sciencesphysical sciencesopticsmicroscopy
- natural sciencesbiological sciencesbiochemistrybiomoleculeslipids
- natural scienceschemical sciencesanalytical chemistrymass spectrometry
- natural sciencesphysical sciencesopticsspectroscopy
Palabras clave
Programa(s)
Régimen de financiación
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinador
21000 Split
Croacia