Objective
While it is has long been noted that genome stability is a central function required for survival of stem cells, the role of protein homeostasis (proteostasis) has not been explored. With the asymmetric divisions invoked by stem cells, the passage of damaged proteins to daughter cells can destroy the resulting lineage of cells and possibly accelerate the aging process. Furthermore, the possible retention of damaged proteins by the stem cell can result in diminished stem cell function and possibly premature aging. Therefore, a firm understanding of how stem cells maintain their proteostasis is of central importance. Because experiments with mammalian embryonic stem cells have clearly demonstrated their capacity to replicate continuously in the absence of senescence, we hypothesize that these cells could provide a novel paradigm to study the regulation of proteostasis and its demise in aging. We have recently described that human embryonic stem cells (hESCs) exhibit high proteasome activity compared to their differentiated counterparts. This enhanced proteasome activity is necessary for hESC function. Furthermore, we have uncovered that PSMD11/rpn-6, a key proteasomal subunit, is required for this activity and its mode of regulation and conservation in the aging process of the invertebrate C. elegans. Moreover, ectopic expression of rpn-6 protects from the symptoms associated to Huntington’s disease. We hypothesize that, in addition to its regulation of the proteasome, hESCs must differentially regulate multiple subcellular stress response pathways designed to protect the hESC from disequilibrium in the synthesis, folding, and degradation of its proteome. In this work, we will: 1) define the mechanisms by which enhanced proteasome activity controls hESC function; and 2) determine how other proteostasis pathways impinges upon hESC function 3) with an eye to understand how this network can be adapted to alleviate age-related pathologies such as Huntington’s disease.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciences biological sciences biochemistry biomolecules proteins proteomics
- medical and health sciences medical biotechnology cells technologies stem cells
- medical and health sciences basic medicine pathology
- natural sciences biological sciences genetics genomes
- medical and health sciences basic medicine physiology homeostasis
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2013-CIG
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Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
MC-CIG - Support for training and career development of researcher (CIG)
Coordinator
50931 KOLN
Germany
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.