Objective
Replication stress has emerged as a prominent driver of genomic instability. The ATR kinase is a master regulator of the cellular response to replication stress and defects in ATR activation or loss of its signaling components leads to DNA damage, genomic instability and tumorigenesis. Yet the direct mechanisms by which ATR signaling prevents these repercussions remain poorly understood. The primary aim of this study is to investigate a novel role for ATR in regulating the cellular replication timing program and corresponding gene expression. I hypothesize that replication stress caused by disruption of ATR signaling perturbs the carefully regulated timing by which genes are replicated. This directly alters gene expression patterns, potentially leading to oncogene activation and/or silencing of tumor suppressors. This idea is substantiated by my preliminary results indicating striking shifts in replication timing of select genomic loci under defective ATR signaling. Furthermore, a recent finding that ATR maintains the transcriptional status of genes in the vicinity of stalled forks alludes to a similar connection. This timely study will be the first to identify genes with altered transcriptional activity as a result of perturbations in replication timing under ATR-mediated replication stress. Functional characterization of these gene products will provide new insight into how ATR determines replication timing and direct mechanistic basis for how ATR signaling safeguards against tumorigenesis. The outcomes can better inform exploitation of replication stress in cancer therapeutics in the form of ATR inhibitors and underlying pathologies in ATR-deficient Seckel syndrome and associated hereditary diseases. By bridging the fields of replication stress and timing, I will gain new skills in transcriptomics, chromatin biology and in vivo tumor models to complement my previous expertise in replication timing and genomics, laying strong foundations for my independent career.
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
- medical and health sciences basic medicine pathology
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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.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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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) H2020-MSCA-IF-2016
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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.