Objective
Eukaryotic translation initiation is a process wherein ribosomal subunits are assembled by eukaryotic initiation factor (eIF) proteins. Mammalian eukaryotic translation initiation factor 3 (eIF3), consisting of the 13 subunits eIF3a to eIF3m, is the largest and most complex eIF. Due to the emerging understanding of the role of eIF3 in a wide range of cancers, there is an increasing interest to examine its many subunits as potential therapeutic targets. Furthermore, interactions between subunit eIF3c and tumor suppressor protein schwannomin has been reported to promote development of the tumor neurofibromatosis 2 (NF2). Very few small molecule inhibitors reported targeting eIF3 subunits are reported, and are associated with high degree of uncertainty. There is hence a need to develop new and highly effective small molecules targeting the eIF3 subunits to be used in the treatment of cancer, as well as in the fundamental understanding of the interactions between the various subunits.
The aim of this interdisciplinary project is to investigate the structures, dynamics, and interactions of subunits in the eIF3 family, and use this information to design, synthesize and test compounds for targeted cancer therapy. We will employ a range of computational and bioinformatics-based tools (protein-protein docking, molecular dynamics and metadynamics simulations, machine-learning based ligand design and docking techniques) to identify and explore key druggable interactions and regions in the initially targeted subunits eIF3a and c. To verify the inhibitory potential of the designed small molecules, chemical synthesis and in vitro evaluation will be performed. Through the combination of computational modeling, subunit-specific inhibition, and measurements of anticancer activity, we will be able to understand in more detail the mechanisms of action as well as interplay between different subunits, and the interactions between eIF3c and tumor suppressor protein schwannomin.
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
- medical and health sciences clinical medicine oncology
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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-2023-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.
405 30 Goeteborg
Sweden
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.