Project description
Targeting telomere maintenance in cancer
Telomeres are protective caps at the ends of chromosomes that maintain genome stability. Most cancer cells maintain telomeres by reactivating an enzyme called telomerase. However, 10-15 % of cancers including aggressive types such as osteosarcoma and glioblastoma use an alternative pathway called alternative lengthening of telomeres (ALT), which maintains telomere length through a DNA repair process. This allows cancer cells to divide indefinitely. Supported by the Marie Skłodowska-Curie Actions programme, the RBPandALT project aims to investigate the role of RNA-binding proteins in regulating ALT activity. The goal is to identify RNA-binding proteins that influence telomere stability in ALT-positive cancers, characterise their mechanisms of action and evaluate their potential as therapeutic targets. Project findings could open new avenues for treating aggressive tumours.
Objective
Telomeres are protective structures at chromosome ends that prevent genome instability. In most cancer cells, telomere shortening is counteracted by telomerase reactivation. However, 10–15% of cancers, including aggressive types like osteosarcoma and glioblastoma, use a telomerase-independent pathway known as Alternative Lengthening of Telomeres (ALT). ALT relies on homology-directed DNA repair and is triggered by persistent replication stress at telomeres. Despite recent advancements in cancer therapy, ALT+ cancers currently lack targeted therapies and have a poor prognosis, highlighting the need to increase our understanding of ALT and develop new treatments against these aggressive tumours.
Increasing evidence suggests a role of RNA-binding proteins (RBPs) in DNA replication stress response and telomere stability. Therefore, I hypothesise that a subset of RBPs influence telomere replication stress and can modulate ALT activity. Towards this, I plan to:
1) Perform a CRISPR-based screen in ALT-positive and ALT-negative cancer cell lines to identify RBPs that affect telomeric replication stress and ALT activity.
2) Study how top candidate RBPs regulate telomere replication stress and ALT-specific telomere DNA synthesis using a range of molecular assays.
3) Evaluate the therapeutic potential of targeting these RBPs in ALT-positive cancers by testing their effects on cell viability and response to DNA damaging agents.
This work will reveal new RBP regulators of ALT and provide insight into the interplay between RNA metabolism, replication stress, and telomere maintenance. This project will provide a deeper, mechanistic understanding of how RNA-binding proteins influence telomere replication stress and ALT, filling a critical gap in telomere biology and paving the way for innovative cancer treatments against these aggressive tumours.
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 genetics DNA
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences genetics RNA
- natural sciences biological sciences genetics chromosomes
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.
NW1 1AT London
United Kingdom
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.