Projektbeschreibung
Dem Rätsel des Alterns auf der Spur
Um die ursächlichen Mechanismen der Zellalterung ranken sich zahlreiche Theorien, die den Prozess auf DNS-Schäden und oxidative Schäden an Proteinen zurückführen. Über die genaue Ätiologie ist bislang jedoch nur wenig bekannt. Ziel des EU-finanzierten Projekts CarboPore ist es, die Beteiligung von oxidativ geschädigten Proteinen an der Zellalterung zu untersuchen. Die Forschenden werden von der Hypothese ausgehen, dass altersassoziierte Proteinaggregate Membranschäden und -permeabilisierung auslösen. Um diese Frage zu klären, werden sie mithilfe fortschrittlicher bildgebender und biochemischer Verfahren untersuchen, wie sich Proteinaggregate auf die Zellmembranintegrität auswirken. Die Ergebnisse des Projekts werden neue zelluläre und molekulare Erkenntnisse über das Altern hervorbringen, die diesen komplexen Prozess weiter entschlüsseln werden.
Ziel
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.
Wissenschaftliches Gebiet
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- natural sciencesphysical sciencesopticsmicroscopy
- natural sciencesbiological sciencesbiochemistrybiomoleculeslipids
- natural scienceschemical sciencesanalytical chemistrymass spectrometry
- natural sciencesphysical sciencesopticsspectroscopy
Schlüsselbegriffe
Programm/Programme
Thema/Themen
Aufforderung zur Vorschlagseinreichung
Andere Projekte für diesen Aufruf anzeigenFinanzierungsplan
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Koordinator
21000 Split
Kroatien