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Nuclear envelope attachment and dynamics of Human telomeres - unravelling nuclear organization

Objective

The spatial and temporal organization of the nucleus and its components are essential for genome regulation. During interphase of mammalian cells the nuclear envelope maintains the shape and the mechanical integrity of the nucleus, but also provides an anchor for chromatin that is connected to its inner side. This interaction mediates the regulation of gene expression, DNA replication and the maintenance of genome stability. In human cells I found that a large subset of telomeres, the natural ends of linear chromosomes, are transiently anchored to the nuclear envelope specifically during postmitotic nuclear assembly. Chromatin organization undergoes extensive changes during progression through the cell cycle, particularly during mitosis with the nuclear envelope breakdown and the compaction of chromatin into metaphase chromosomes. The interaction between chromosome ends and the nuclear envelope at the stage where the nucleus is reforming post-mitosis suggests a new role for telomeres in nuclear organization. My aims are 1) to screen for interacting partners that mediate the cell-cycle dependent telomere tethering to the nuclear membrane; 2) to unravel the molecular mechanism of telomere-nuclear envelope association over the cell cycle by combining biochemistry and state-of-the-art microscopy; 3) to map the subset of chromosomes which ends are tethered using subtelomere specific FISH probes and determine whether they are conserved throughout cell divisions and if it plays a role in organizing chromosome territories; 4) to examine telomere dynamics in cells from premature aging syndromes affecting the nuclear envelope integrity using live imaging confocal microscopy, and understand the connection between telomeres, nuclear envelope, and aging. The originality of my scientific approach is to combine state-of-the-art cell biology, biochemistry, and molecular biology for an integrated view of human telomere function in nuclear organization.

Fields of science (EuroSciVoc)

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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)

Programme(s)

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Topic(s)

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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.

ERC-STG - Starting Grant

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2016-STG

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Host institution

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Net EU contribution

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.

€ 1 795 010,00
Address
RUE MICHEL ANGE 3
75794 PARIS
France

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Region
Ile-de-France Ile-de-France Hauts-de-Seine
Activity type
Research Organisations
Links
Total cost

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.

€ 1 795 010,00

Beneficiaries (1)

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