Objective
The self-renewing nature of stem cells is a consequence of their ability to proliferate indefinitely while maintaining pluripotency. Mechanisms of pluripotency are well known but mechanisms controlling stem cell proliferation are unknown. Proliferation of somatic cells takes place in G1 cell cycle phase. We have identified that embryonic and peripheral neural stem cell proliferation is regulated by an entirely new mechanism involving chromatin remodeling and operating in the S/G2 phase of the cell cycle (Andang et al., Nature 2009). This involves the DNA damage response (DDR) pathway proteins. The DDR pathway is activated physiologically by GABA acting by the GABAA receptor leading to Cl- influx, cell swelling, and by unknown mechanism, activation of the PI3K related kinases ATR/ATM which phosphorylates histone H2AX. Combined, the data suggests that the DDR pathway is operating in a ligand-dependent manner under normal physiological conditions and that it may serve as a new molecular mechanism regulating cell proliferation in eukaryotic cells. We propose a homeostatic mechanism of stem cell proliferation where negative feedback control of the cell cycle adjusts stem cell numbers. The demonstration of normal, physiological, ligand-induced activation of these pathways in stem cell niches opens fundamentally new insight into the mechanisms of stem cell proliferation and surveillance against cancer. Once characterized, we propose that these mechanisms may be exploited to induce self repair following brain damage and to manipulate cell survival in tumor initiating cells of the brain (that share many characteristics with stem cells). The potential benefit of this proposed research could be vast, involving potentially a unifying mechanism how all stem cell niches in the embryo and in the adult individual is regulated and can be manipulated.
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 genetics DNA
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences medical biotechnology cells technologies stem cells
- medical and health sciences clinical medicine oncology
- medical and health sciences clinical medicine embryology
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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.
ERC-2008-AdG
See other projects for this call
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.
Host institution
171 77 STOCKHOLM
Sweden
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.