Objective
PROteolysis TArgeting Chimera (PROTAC) is a new and attractive therapeutic approach that regulates a target protein by channeling it to the proteasome for degradation (an energy-demanding pathway). Concurrently, proteasomes also play a central role in generating the peptide repertoire for antigen presentation on the Human Leukocyte Antigen-I (HLA-I) molecules. A few years after PROTAC was invented, proteasomes were found to catalyze not only canonical peptide bond hydrolysis, but are also capable of “cut-and-paste” events, i.e. generating spliced peptides, which have been shown to be frequently presented n HLA-I immunopeptidomes. It is unclear how PROTAC-driven proteasome degradation modulates the spliced and non-spliced peptide repertoire derived from a targeted protein. Alterations in peptide variety and quantity produced by proteasome may lead to strong implications on the HLA-I immunopeptidome, and, hence, could result in immune implications. Therefore, using the key oncoprotein KRAS as a PROTAC’s target, this study intends to understand: (i) how PROTAC-driven KRAS degradation affects cellular pathways on a system-wide level; (ii) the impact of PROTAC on KRAS derived peptide repertoire generated by proteasomes; (iii) to what extent PROTAC enhances KRAS derived peptide presentation on HLA-I molecules. Through the combination of a multidisciplinary approach; molecular biology, biochemistry, proteomics, bioinformatics and cellular immunology, this study will provide a better fundamental understanding of the effect of PROTAC-KRAS on the cellular proteome, proteasome-derived peptide repertoire (spliced and non-spliced peptides) and HLA-I immunopeptidome landscape, thus, provide insights into the suitability of PROTAC-KRAS application as a therapeutic approach for anti-cancer therapies. Additionally, this project will deepen our understanding of the role of spliced peptides in the antigen processing and presentation pathway.
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 proteomics
- medical and health sciences basic medicine immunology
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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-2021-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.
80539 MUNCHEN
Germany
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.