Project description
A novel genome-editing tool
Discovery of the genome-editing ability of bacteria through the CRISPR-Cas system has revolutionised genome editing. However, limitations associated with off-target effects hamper the exploitation of CRISPR-Cas for medical applications. The EU-funded MIGHTY_RNA project is investigating the molecular mechanism of Tetrahymena thermophila DNA elimination as an alternative genome-editing approach. Researchers will determine how the eukaryotic RNA system (Twi1) that mediates this DNA elimination in ciliates recognises and cuts its target sequences. The MIGHTY_RNA study has the potential to create a new genome-editing tool that can outperform CRISPR-Cas in various applications.
Objective
Genome editing is an essential tool for life sciences. Recent ground-breaking discovery in microbiology drew our attention to the genome editing ability of bacteria (CRISPR). Since its discovery, CRISPR has revolutionized the way of editing a genome. Despite its wide use, CRISPR-genome editing has limitations, especially in the use for medical applications. Numerous studies have shown that it suffers from the off-target effect. Its use is also restricted by its particular sequence requirement and its poor accessibility to a structured genome. Furthermore, recent studies suggested that it might act as a virulence factor within human cells. These limitations demand new genome editing tools.
This proposal sets out to understand the molecular mechanism of Tetrahymena DNA elimination. This naturally occuring genome editing is mediated by a eukaryotic RNA system (Twi1). This system uses an entirely different mechanism from CRISPR and has potential to perform more effectively. I will first investigate how small RNA-loaded Twi1 (“target searcher”) recognizes its target and whether its performance exceeds other target searchers including CRISPR/Cas9. I will use single-molecule fluorescence for high resolution observations and develop a high-throughput single-molecule method for transcriptome-wide understanding. Second, I aim to identify a Twi1-related DNA nuclease(s) that carries out DNA elimination. I will use cutting-edge tools of single-molecule pull-down and multi-color FRET together with mass spectrometry. The nanoscopic understanding of a searcher (Twi1) and the identification of a nuclease will help create a new genome editing tool (e.g. a fusion of Twi1 and the nuclease) that potentially perform better than Cas9. Thereby, this fundamental study on “mighty RNA” will make a long-term impact for applications in science and technology. To realize this ambitious project, I will utilize my experience of studying small RNAs (funded by ERC Starting Grant).
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- medical and health sciences medical biotechnology genetic engineering gene therapy
- natural sciences biological sciences genetics DNA
- natural sciences biological sciences genetics RNA
- natural sciences chemical sciences analytical chemistry mass spectrometry
- natural sciences biological sciences genetics genomes
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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.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
MAIN PROGRAMME
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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
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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.
ERC-COG - Consolidator Grant
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2018-COG
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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.
2628 CN DELFT
Netherlands
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