Objective
Ribosomal DNA (rDNA) encodes the ribosomal RNAs essential for protein synthesis and thus for cell growth and maintenance. Owing to its repetitive nature, high GC content, and intense transcriptional activity, rDNA is among the most fragile genomic regions and is normally safeguarded by a specialized nucleolar DNA damage response (n-DDR). In senescent cells, however, persistent rDNA damage accumulates, coinciding with genomic instability and the chronic activation of inflammatory signaling pathways that drive the senescence-associated secretory phenotype (SASP). SASP has strong tumour-promoting effects and contributes to malignancy and therapy resistance. Despite these observations, the causes of persistent rDNA damage in senescence and its connection to genome instability and SASP remain poorly understood.
This project will address this critical gap by investigating whether the profound remodeling of the nucleolus during senescence, including structural reorganization and rRNA hyper-transcription, impairs the fidelity of n-DDR and compromises rDNA stability. Using an oncogene-induced senescence model, I will pursue three objectives: (1) test how nucleolar reorganization and elevated rRNA transcription affect n-DDR fidelity using advanced imaging and quantitative proteomics, (2) identify structural alterations and mutational signatures that accumulate at rDNA loci through long-read sequencing and computational analysis, and (3) establish the causal link between rDNA damage and SASP activation by applying genomic approaches and targeted perturbations.
This project will deliver the first mechanistic framework for nucleolar genome instability in senescence. Beyond advancing our understanding of genome maintenance, it may reveal novel biomarkers of senescence and uncover therapeutic opportunities to reprogram or suppress the pro-cancerous activities of senescent cells, thereby contributing to strategies that reduce cancer burden.
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.
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.
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences genetics RNA
You need to log in or register to use this function
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.
2100 Koebenhavn
Denmark
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.