Objective
DNA replication is an essential process for genome duplication, cell division and ultimately organismal survival that ensures faithful transmission of the genome to progeny. Certain genomic loci represent major obstacles to DNA replication including fragile sites, G-rich tracts and repetitive sequences, such as ribosomal DNA and telomeres. Mammalian telomeres have the propensity to adopt complex DNA secondary structures, including telomere-loops and telomeric G-quadruplex DNA, which are believed to play essential roles in telomere maintenance. However, recent work has established that these structures are also a hindrance to DNA replication and failure to stabilise, repair or restart the replication fork is a potential source of genome instability, the hallmark of many diseases including cancer.
Despite recent advances, the mechanisms that facilitate DNA replication at telomeres and other hard to replicate loci throughout the genome remain unclear. This proposal aims to address this important question in order to discover and decipher the mechanisms that help DNA replication through DNA secondary structures. I propose using multidisciplinary approaches to investigate the cellular response to replication stress at telomeres and the enzymatic activities that result in telomere replication aberrations, which will involve direct visualisation of telomere abnormalities using complementary DNA related methodologies and analysis of novel telomere-associated complexes. I also plan to determine the nature/structure of fragile telomeres, which remains poorly defined and represent a central question for the field using visualisation of biological molecules and proteomics.
The detailed investigation of the function of known and new factors that facilitate telomere DNA replication represent an outstanding challenge that will provide a novel framework for understanding the contributions of replication factors in general DNA replication, genome stability and cancer in humans.
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciences biological sciences genetics DNA
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences genetics chromosomes
- medical and health sciences basic medicine neurology
- natural sciences biological sciences genetics genomes
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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
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2014-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.
SW7 2AZ 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.