Project description
Advanced genome editing tools
The CRISPR-Cas, originally discovered as a bacterial immune system, is a highly effective gene-editing tool for targeted DNA modifications. The system edits a genomic sequence by creating double-stranded breaks in the DNA and then taking advantage of cellular DNA repair pathways. However, this limits its application to dividing cells. With the support of the Marie Skłodowska-Curie Actions programme, the CASTedit project proposes to repurpose CRISPR-associated transposons (CASTs) for gene editing purposes. CASTs are programmable mobile genetic elements that insert large DNA cargos using an RNA-guided mechanism without the need for double-strand breaks. Researchers will employ cutting-edge technologies to engineer and validate CASTs in mammalian cells, opening new frontiers in regenerative medicine, cell engineering, and gene therapy.
Objective
The rapid advancements in CRISPR-Cas technology have revolutionized gene editing, yet significant challenges persist, particularly the reliance on DNA Damage Response (DDR) pathways and the limitations in integrating large DNA segments. These constraints hinder the application of CRISPR-Cas systems, especially in non-dividing cells and complex genomic modifications. The recently discovered CRISPR-associated transposon (CAST) systems offer a transformative solution, enabling the insertion of large DNA cargos (10–30 kb) into specific genomic locations without inducing double-strand breaks (DSBs), thereby providing a safer and more versatile genome-editing tool. The CASTedit project aims to repurpose CAST systems as next-generation genome editing tools, with a focus on mammalian cells. Specific objectives include the development of engineered CAST systems (Types V-K and I-D) for precise DNA integration, the exploration of novel CAST complexes for RNA-guided transposition, and their validation at the organismal level. Successful implementation of these systems in eukaryotic cells could overcome current CRISPR limitations, paving the way for innovative applications in cell engineering, regenerative medicine, and biotechnology. Under the guidance of Prof. Guillermo Montoya, a leading expert in the structure-function analysis of nucleases, and with his pioneering research in CAST complex assembly at the University of Copenhagen, I will be well-positioned to achieve the goals of this project. I will leverage my expertise in CRISPR-based genome editing, protein expression systems in eukaryotes, and high-throughput mutant screening to optimize CAST systems for precise DNA integration in mammalian cells. The successful execution of CASTedit will establish me as a prominent researcher in genome engineering, utilizing the host institution’s state-of-the-art facilities and collaborative environment to drive innovation in therapeutic applications.
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 genetics DNA
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences genetics genomes
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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)
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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)
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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.
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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
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(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.
1165 KOBENHAVN
Denmark
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