Project description
Unveiling the mysteries of ageing
There are many theories on the underlying mechanisms of cellular ageing implicating DNA damage as well as oxidative damage to proteins. However, the precise aetiology remains poorly understood. The scope of the EU-funded CarboPore project is to investigate the contribution of oxidatively damaged proteins to cellular ageing. Researchers will work under the hypothesis that age-associated protein aggregates cause membrane damage and permeabilisation. For this purpose, they will assess the impact of protein aggregates on cellular membrane integrity using advanced imaging and biochemical techniques. The project's results will unveil novel cellular and molecular aspects of ageing, shedding light on this complex process.
Objective
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.
Fields of science
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- natural sciencesphysical sciencesopticsmicroscopy
- natural sciencesbiological sciencesbiochemistrybiomoleculeslipids
- natural scienceschemical sciencesanalytical chemistrymass spectrometry
- natural sciencesphysical sciencesopticsspectroscopy
Keywords
Programme(s)
Funding Scheme
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinator
21000 Split
Croatia