Objective
G-quadruplex (G4) structures are stable four-stranded nucleic acids assemblies that can form in guanine-rich DNA. Their recent visualization in mammalian cells has established G4 structure formation throughout the genome and fueled research into understanding the biological implications of these structures in cell regulation.
G4 sequence motifs are abundant and conserved in our genome. G4 structures form transiently and regulate numerous cellular processes such as DNA replication, transcription and telomere maintenance. Importantly, these structures also come at a cost as they are able to induce genomic instability in certain cellular conditions, for example in cancer cells that suffer from replication stress.
Currently, the mechanisms that form and resolve G4 structures are unknown. Several helicases can unwind these stable DNA structures in vitro but it is unclear whether and how these helicases function in vivo. Understanding the biochemical mechanisms that resolve G4 structures is crucial to further understand their function and how they induce DNA mutations in the cell.
In this project, I propose to decipher the molecular mechanisms of G4 structures unwinding. The groundbreaking nature of this proposal is the use of a unique method to follow G-quadruplex unfolding in time under near-physiological conditions in vitro. This method, which was recently established in the host laboratory, uses DNA replication stalling and bypass at defined G4 structures as a direct readout for G4 stability and unwinding. This gives me the opportunity to address important aspects that have not been studied under physiological conditions before:
Aim 1: To determine the stability and unwinding properties of distinct G4 conformations.
Aim 2: To identify molecular mechanisms and novel proteins in G4 unwinding.
The results of this project will give important new insights into G4 regulation, an unexplored but important biological process.
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 nucleic acids
- natural sciences biological sciences genetics DNA
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences chemical sciences analytical chemistry mass spectrometry
- 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.1.3. - 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.
1011 JV AMSTERDAM
Netherlands
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.