Project description
Understanding the impacts of beta-catenin condensation
Beta-catenin, or β-catenin, is a key signal-transduction protein that is necessary in the majority of the cells in the body. It plays a critical role in the highly conserved Wnt-signalling pathway, regulating cell fate specification, proliferation and differentiation during development and in various adult tissues. To achieve this role, β-catenin is present at the plasma membrane in the cytoplasm and in the cell nucleus. In all these sites β-catenin needs to be highly localized and organized. How this organization takes place is currently unknown. The EU-funded Catenin-Condensation project aims to uncover how the condensation of β-catenin into protein droplets, at the membrane and in the cytoplasm, impacts the Wnt signalling pathway. The proposed work will contribute to understanding cancer etiology. What is more, deeper knowledge of the fundamental Wnt signalling pathway can have a profound impact on the understanding of embryonic development, adult regeneration and cancer.
Objective
The Wnt-signaling pathway is a key determinant of cell identity and proliferation. However, when aberrantly activated it drives malignant cell proliferation in gastrointestinal cancer, breast cancer, melanoma and leukemia. The key effector protein of the Wnt pathway is β-catenin, which is continuously degraded in unstimulated cells, but in stimulated cells it accumulates and translocates to the nucleus where it activates transcription. A growing body of literature indicates that transcription factors and co-activators interact through the formation of biomolecular condensates. These are membraneless organelles that concentrate and compartmentalise components through weak, but multivalent interactions. Recently, I have shown that β-catenin forms condensates with Mediator co-activator to specifically activate transcription. However, how this new mode of β-catenin interactions influences the rest of the Wnt-pathway is currently unknown. The overarching goal of this proposal is to uncover how β-catenin condensation impacts the Wnt-signaling pathway. I will investigate the consequences of β-catenin condensation for its cytoplasmic regulation by the destruction complex, study how it affects β-catenin co-factor interactions in the nucleus and determine the effect of oncogenic Wnt-signaling on β-catenin condensates. The proposed work will uncover if β-catenin condensation has a function in the Wnt-signaling pathway outside the nucleus, its effect on co-factor interactions and elucidate how it might contribute to cancer etiology. Deeper understanding of the fundamental Wnt-signaling pathway will have a profound impact on our comprehension of embryonic development, adult regeneration 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.
- medical and health sciences clinical medicine oncology skin cancer melanoma
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences developmental biology
- medical and health sciences clinical medicine oncology breast cancer
- medical and health sciences clinical medicine oncology leukemia
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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.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
MSCA-IF-EF-RI - RI – Reintegration panel
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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) H2020-MSCA-IF-2019
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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.
3584 CX Utrecht
Netherlands
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