Objective
Alterations in chromosome number and size are hallmarks of cancer, and yet they are also crucial for species evolution. Recent insight on chromosome structure and segregation, together with significant advances in genomic sequencing, established previously underappreciated parallels between the mechanisms of karyotypic evolution during speciation and cancer. Importantly, alterations in chromosome number and size pose significant challenges for the cell division machinery. However, how dividing cells adapt to cope with karyotypic alterations remains an outstanding fundamental question with strong clinical implications. To address this, we propose an innovative approach that integrates super-resolution microscopy, large-scale 3D cryo-electron tomography reconstructions, computational modelling and cell fusion experiments in Indian and Chinese muntjacs, two closely related deer species with identical genomes, but extremely divergent chromosome number (2n=6/7 vs. 2n=46, respectively) and size. We will focus on dissecting mechanistic aspects underlying mitotic spindle organization, chromosome dynamics, checkpoint control of mitotic progression and segregation fidelity in both muntjac species, with the goal of identifying genes differentially required for efficient mitosis in cells with karyotypic alterations. In parallel, we will exploit functional genomics in Cervidae, including telomere-to-telomere sequencing of Indian and Chinese muntjac genomes, to determine and manipulate the exact chromosome fusion sites between both species, while testing the novel hypothesis of a viral mechanism in the evolution of their karyotypes. Lastly, to test the limits of karyotypic evolution for chromosome segregation, we will engineer mammalian cells with only 1 or 2 chromosomes and investigate whether and how cell division tolerates this extreme genome reorganization. This pioneer work will unveil vital cell adaptive mechanisms to karyotypic evolution relevant for speciation and cancer.
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 physical sciences optics microscopy super resolution microscopy
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences genetics chromosomes
- 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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HORIZON.1.1 - 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.
HORIZON-ERC - HORIZON ERC Grants
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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-2023-ADG
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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.
4200-135 PORTO
Portugal
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.