Project description DEENESFRITPL Protein homeostasis mechanisms during ageing Proteins are central to all biological processes but are prone to misfolding, aggregation and damage, particularly as cells age. Proteostasis mechanisms, such as those involving chaperones and proteolytic systems like the proteasome, work together to monitor protein quality and repair or remove damaged or misfolded proteins. Funded by the European Research Council, the StemProteostasis project focuses on the role of the proteasome in human embryonic stem cell (hESC) function. Researchers will investigate different proteostasis pathways in hESCs and somatic cells to understand how they impact stem cell exhaustion and tissue degeneration. Project findings will also provide important insight into the role of proteostasis in ageing and age-related diseases. Show the project objective Hide the project objective Objective By 2050, the global population over the age of 80 will triple. Thus, research for improving the quality of life at older age can be of enormous benefit for our ever-aging society. To address this challenge we propose an innovative approach based on a combination of stem cell research with genetic experiments in C. elegans. Mechanisms that promote protein homeostasis (proteostasis) slow down aging and decrease the incidence of age-related diseases. Since human embryonic stem cells (hESCs) replicate continuously in the absence of senescence, we hypothesize that they can provide a novel paradigm to study proteostasis and its demise in aging. We have found that hESCs exhibit increased proteasome activity. Moreover, we have uncovered that the proteasome subunit RPN-6 is required for this activity and sufficient to extend healtshpan in C. elegans. However, the mechanisms by which the proteasome regulates hESC function remain unknown. Our first aim is to define how the proteasome regulates not only hESC identity but also aging and the onset of age-related diseases. Moreover, one of the next challenges is to define how other proteostasis pathways impinge upon hESC function. We hypothesize that, in addition to the proteasome, hESCs differentially regulate other subcellular stress response pathways designed to protect them from disequilibrium in the folding and degradation of their proteome. We will perform a comprehensive study of proteostasis of hESCs and mimic this network in somatic cells to alleviate age-related diseases. Finally, we will determine whether loss of proteostasis promotes somatic stem cell (SC) exhaustion, which is one of the most obvious characteristics of the aging process and contributes to tissue degeneration. By using mouse models we will examine whether sustained proteostasis delays neural SC exhaustion. Our research will have an impact in several fields such as stem cell research, neurogenesis, proteostasis, aging and age-related diseases. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomicsmedical and health sciencesmedical biotechnologycells technologiesstem cellsnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsprotein foldingmedical and health sciencesbasic medicinephysiologyhomeostasisnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-StG-2015 - ERC Starting Grant Call for proposal ERC-2015-STG See other projects for this call Funding Scheme ERC-STG - Starting Grant Host institution UNIVERSITAT ZU KOLN Net EU contribution € 1 500 000,00 Address ALBERTUS MAGNUS PLATZ 50931 Koln Germany See on map Region Nordrhein-Westfalen Köln Köln, Kreisfreie Stadt Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 500 000,00 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all UNIVERSITAT ZU KOLN Germany Net EU contribution € 1 500 000,00 Address ALBERTUS MAGNUS PLATZ 50931 Koln See on map Region Nordrhein-Westfalen Köln Köln, Kreisfreie Stadt Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 500 000,00
