Objective
DNA replication is an essential process ensuring the transmission of genetic information and is highly regulated. Specifically, the DNA replication-timing program ensures that the sites of initiation of DNA replication, termed origins, are not all activated simultaneously but follow a cell-type specific schedule. This pathway is conserved throughout eukaryotic evolution, however its molecular control and biological role are not fully understood. In this proposal I aim to understand key aspects of replication-timing program by employing a combination of advanced mouse genetics, genomics, cell biology and proteomics. Currently one of the major limitations in the mammalian DNA replication field is the elusive identity of origins. I aim to comprehensively map origins in a variety of mouse cells/tissues and relate the regulation of origin firing to the control of gene expression and three-dimensional nuclear architecture. I have discovered that Rif1 controls replication timing and links it to nuclear three-dimensional organization. I have also revealed the existence of a novel Rif1-independent pathway that controls the timing of a significant fraction of the late-replicating genome, identified by constitutive association with a key nuclear architecture component, Lamin B1. Here, I propose complementary approaches to understand the molecular mechanism by which Rif1 coordinates replication timing and nuclear organization as well as the molecular underpinnings of the novel pathway instructing late-replication in Lamin B1-associated regions. Finally, my goal is to understand the in vivo biological role of the replication-timing program. Our preliminary data identify mammalian X inactivation as a process where replication timing may play a fundamental part. My ultimate objective is to contribute to the realization of a comprehensive understanding of nuclear function, integrating the co-regulation of DNA replication with gene expression, epigenetic inheritance and DNA repair.
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 proteins proteomics
- natural sciences biological sciences genetics DNA
- 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)
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.
ERC-COG - Consolidator 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-2016-COG
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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.
EH8 9YL Edinburgh
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.