Project description
A new technology for editing large DNA segments
The recent advent of the CRISPR-Cas9 technology has revolutionised targeted genome editing by generating small insertions and deletions at the target site. The EU-funded GenDels project will work on an alternative CRISPR-based technology that employs the Cas3 enzyme which combines helicase and nuclease activity. The aim is to achieve high-throughput gene-editing of large DNA segments in human cells for health-related applications or to decipher the role of non-coding DNA variants in disease. Moreover, this technology could be exploited for the editing of bacterial cells for synthetic biological and metabolic purposes.
Objective
The advent of the revolutionary genome editing technique CRISPR-Cas9 has enabled targeted gene mutation, repression, and activation, facilitating impactful biological findings. However, Cas9 as an unbiased DNA deletion tool is limited in its ability to interrogate large regions of DNA of unknown function, because it predominantly generates very small (<20 bp) insertions and deletions at its target site. The capacity to rapidly and efficiently generate large genomic deletions does not currently exist and would be an extremely useful tool for research, allowing for rapid strain engineering of bacterial cells for synthetic biological and metabolic engineering purposes. Additionally, this technology would allow for the interrogation of large segments of non-coding DNA in human cells, much of which has unknown function, but whose variants are often associated with human disease. In this proposal, I aim to develop a Type I-C CRISPR-Cas system employing the Cas3 enzyme (completely distinct from Cas9), which naturally possess coupled nuclease and helicase activity, for high-throughput gene-editing purposes in various prokaryotic, as well as human cells. My preliminary results have shown that this is a credible approach, as I have been able to generate individually, as well as in combination, multiple deletions in bacterial organisms exceeding 60 kb in size. A focal point of the proposal is to adapt this system for use in human cells, which would provide a novel basic research tool with unprecedented capabilities and also could be utilized in human health-related applications. The proposal aims to address this later possibility by utilizing the developed system to treat human cell lines infected with difficult-to-treat pathogenic viruses.
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 microbiology virology
- natural sciences biological sciences genetics DNA
- natural sciences biological sciences genetics mutation
- natural sciences biological sciences genetics genomes
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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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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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)
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.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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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-2018
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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.
69117 Heidelberg
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.