Objective
DNA replication is essential for the perpetuation of life and, yet, it is also a major source of genomic instability that can lead to cancer and other human diseases. Despite the vast efforts invested in establishing the origins of genomic instability, the mechanisms that coordinate faithful genome duplication while ensuring its integrity remain unknown.
This dilemma is molecularly best exemplified by single stranded DNA (ssDNA), which inevitably results from unwinding the double helix due to replication fork progression, but is at the same time a vulnerable intermediate that can lead to severe genomic lesions. Thus, maintaining an appropriate balance of ssDNA is a paramount challenge for replicating cells. My own work has significantly contributed to this concept by showing that eukaryotic cells have limited resources to guard its ssDNA, and that exhaustion of these resources (due to increased overall levels of ssDNA) causes a lethal fragmentation of the genome termed ‘replication catastrophe’ (RC). To prevent this terminal scenario, ssDNA levels and DNA replication activity must be constrained by yet uncharacterized mechanisms. In eukaryotes, where DNA is simultaneously replicated at multiple sites throughout the genome, this represents a particularly challenging task. Understanding how this is molecularly accomplished could transform our view of the very principles of DNA replication regulation, and also reveal potential therapeutic avenues to exploit RC in the treatment for cancer.
With the present proposal I will address this challenge by investigating how ssDNA maintenance is enrooted in the regulatory principles of DNA replication. I will dissect the mechanisms that, globally and locally, constrain replication activity to prevent genomic instability. By using novel and innovative analytical tools, I aim to provide an unmatched picture of the DNA replication apparatus and to identify novel anticancer strategies based on provoking RC selectively in tumor cells.
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
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences genetics genomes
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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.
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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
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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.
ERC-STG - Starting Grant
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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) ERC-2015-STG
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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.
1165 KOBENHAVN
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.