Objective
Accurate chromosome distribution during mitosis requires that each pair of sister chromatids attaches to microtubules from opposite spindle poles via centromere-based kinetochores. However, incorrect kinetochore-microtubule attachments can be formed. These errors must be corrected to prevent chromosome missegregation and the resulting aneuploidy, an abnormal chromosome count characteristic of most human cancers. Error correction relies on the centromere/kinetochore-localised kinase Aurora B, which promotes the depolymerisation of kinetochore-binding microtubules in response to lack of tension within erroneous attachments. Tension locally modulates the accessibility of Aurora B to its substrates, which include the microtubule-depolymerising motor MCAK. Paradoxically, Aurora B suppresses MCAK activity and should, therefore, stabilise erroneous tensionless attachments. This contradiction nurtures the ambiguity of the long-sought error correction mechanism. Findings from the host laboratory provide new insights into this process. Microtubule poleward flux, driven by motor-mediated sliding of interpolar microtubules, suppresses MCAK depolymerising activity, potentially by generating tension within attachments. My goal is to provide a precise and integrative mechanism on how motor proteins modulate the error correction mechanism. I will focus on three key objectives: (1) identifying the flux-generating motors that create tension within attachments, (2) determining the role of tension in MCAK-mediated error correction, and (3) dissecting the tension-related interplay between Aurora B and MCAK during error correction. To achieve this, I will integrate super-resolution live cell imaging with acute protein depletion using the auxin-degron system, delivered at endogenous loci through CRISPR-Cas9. This approach will enable the monitoring of multiple motors in error correction with unprecedented spatiotemporal resolution, providing new insights into how cells prevent aneuploidy.
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
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences clinical medicine oncology
- 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-2024-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.
2100 Koebenhavn
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.