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Deciphering the mechanism of cellular aging: interaction of oxidatively damaged proteins with the cellular membranes

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.

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Topic(s)

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Funding Scheme

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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2019

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Coordinator

MEDITERANSKI INSTITUT ZA ISTRAZIVANJE ZIVOTA
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 147 463,68
Address
MESTROVICEVO SETALISTE 45
21000 Split
Croatia

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Region
Hrvatska Jadranska Hrvatska Splitsko-dalmatinska županija
Activity type
Research Organisations
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 147 463,68
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