Project description
How chromatin compaction is linked to stem cell quiescence
Stem cells are essential to tissue development and regeneration throughout life, with the latter sustained by stem cells in a dormant yet metabolically active state called quiescence. How cells maintain this state over years and how its disruption leads to impaired tissue regeneration capacity, aging, cancer and degenerative disease remain poorly understood. With the support of the Marie Skłodowska-Curie Actions programme, the HerQuLes project aims to investigate how key stress-response transcription factors modulate DNA organisation to keep stem cells dormant. Using cutting-edge live imaging in the model organism Caenorhabditis elegans, HerQuLes could reveal how chromatin structure and cell cycle arrest are coordinated, potentially opening new avenues to prevent age-related decline in regenerative capacity.
Objective
Stem cell pools in our body regulate tissue differentiation in development and remain available during our lifetime for tissue regeneration. These cells exsit in a cell cycle arrested but metabolically active state known as quiescence. Understanding how these cells maintain quiescence and survive over years is fundamental, as its dysregulation impairs regenerative capacity and is linked to ageing, cancer, and degenerative diseases.
The HerQuLes project aims to uncover the mechanisms by which key transcription factors establish and maintain cellular quiescence by studying a novel aspect: the chromatin organization during this state. Preliminary data strongly suggest that two transcription factors involved in the stress response play a pivotal role in modulating chromatin compaction during quiescence. However, the mechanisms by which the cell cycle is blocked remains an open question. To address this, I will use the nematode Caenorhabditis elegans, an excellent model for studying quiescence. Upon starvation, larvae enter in L1 arrest state that resembles mammalian stem cell quiescence. As in mammals, chromatin reorganization and stress-related transcriptional responses occur in arrested L1 larvae.
Using cutting-edge in vivo tools, I will quantify the degree of chromatin compaction, determine which chromatin regions are bound by the transcription factors and study its physical interaction, all under L1 arrest.
Quiescent cells accumulate damage over time, delaying re-entry into the cell cycle and contributing to age-related regenerative decline. European healthcare systems are challenged as the population over 65 is expected to double within the next 35 years, and so do the illnesses associated to ageing. HerQuLes provides mechanistic insights into how quiescence is preserved and opens new targeting avenues to maintain tissue regeneration capacity in older adults, ultimately accelerating healing and reducing the societal and economic burden of ageing-related diseases.
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: The European Science Vocabulary.
This project's classification has been human-validated.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
This project's classification has been human-validated.
- natural sciences biological sciences genetics DNA
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences cell biology
- medical and health sciences medical biotechnology cells technologies stem cells
- natural sciences biological sciences molecular biology structural biology
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.
-
HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
MAIN PROGRAMME
See all projects funded under this programme
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.
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.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
See all projects funded under this funding scheme
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.
(opens in new window) HORIZON-MSCA-2025-PF
See all projects funded under this callCoordinator
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.
41004 Sevilla
Spain
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.