Objective
In the recent years a number of protein systems have been identified that recognize long (tens of base pairs) DNA sequences and allow flexible programmability of their target specificity. This promoted an enormous range of applications in genome engineering and synthetic biology. This project aims to decipher the mechanisms by which these proteins recognize their DNA targets in order to develop quantitative models/predictors for target recognition and to avoid off-target effects.
To obtain detailed insight into the targeting mechanisms of different programmable systems in a “bottom-up manner”, cutting-edge single-molecule experiments, such as mechanical DNA twisting combined with single-molecule fluorescence detection will be employed. This will provide a fully quantitative characterization of the targeting process and insight into the mechanisms of allosteric regulation coupled to targeting. The quantitative data will allow to develop physics-based models of the target recognition process. In particular, we will focus on recognition through non-equilibrium, directional zipping along the target sequence – as recently revealed for CRISPR-Cas enzymes – as a promising unifying mechanism. To obtain precise targeting predictors our first-principle models will be tested and refined using high-throughput measurements on many different targets in parallel. Finally, the predictions will be used in order to understand target selection in live cells using single-molecule imaging.
Within the project the following goals are defined:
Goal 1: Quantitative understanding of target binding/degradation for CRISPR-Cas systems
Goal 2: Detailed mechanistic insight into the target recognition process by TALEs
Goal 3: Development of highly parallelized measurements on different target sequences down to the single-molecule level
Goal 4: Target identification in the complex environment of live cells
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 synthetic biology
- natural sciences biological sciences genetics DNA
- 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.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
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.
ERC-COG - Consolidator Grant
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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) ERC-2016-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.
04109 Leipzig
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.