Objective
Telomeres of eukaryotic chromosomes are protected by the shelterin complex. The human shelterin is a six-subunit protein assembly (TRF1, TRF2, TPP1, POT1, TIN2, Rap1). This complex associates with telomeric DNA and prevents the mistaken detection of the telomeres as double strand breaks by the DNA Damage Response (DDR) machinery. Illicit DNA repair at telomeres results in cell cycle arrest and end-to-end chromosomal fusions or other improper recombinations causing genome instability. The abrogation of the shelterin assembly or subunit removal decompacts the telomere and causes DDR accumulation. Defects in the shelterin complex are associated with telomere-related pathologies such as cancer and aging.
The supra-structure of the mammalian shelterin complex remains unknown. Therefore, we lack fundamental knowledge regarding its organization and function.
The shelterin complex also acts as a signalling hub, recruiting accessory factors that participate in telomere homeostasis and maintenance; and shelterin subunits are subjected to posttranslational modifications (i.e. ubiquitination, phosphorylation, SUMOylation); however, the functional role of these modifications is not fully understood.
The overarching aim of this project is to solve the atomic structure of the human shelterin complex by cryo-EM and elucidate the molecular events of telomere biology during the cell cycle combining cellular and proteomic approaches.
The outcomes will provide the first structure of the shelterin complex and the shelterin interactome, which will allow to understand defects underlying pathology at molecular level and join this information to physiologic and phenotypic data.
This project will have a substantial impact on my career, as new skills in biophysics, structural biology and proteomic techniques on human macromolecular complexes will complement my previous expertise in X-ray crystallography, biophysics, and biochemistry on bacterial and viral proteins.
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
- natural sciences biological sciences genetics chromosomes
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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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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
MAIN PROGRAMME
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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.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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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) HORIZON-MSCA-2021-PF-01
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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.