Project description
A closer look at artificial enzyme evolution
Directed evolution is an effective method for protein engineering that represents one of the most widespread tools in basic and applied biology. The EU-funded GuideArtifEvol project will introduce full-gene next-generation sequencing to supervise the investigation of variants at the sequence level and quantitatively characterise the fitness landscape, focusing on the non-additive effects of mutations on fitness (epistasis). This information will be included in DE protocols to guide a more efficient exploration of the sequence space. The project aims to improve understanding of the topology of the enzyme’s fitness landscape and its distortions under selective pressures and elucidate the correlations between sequence, function, and evolution in proteins.
Objective
Directed evolution is an effective method for protein engineering. The host laboratory is designing innovative techniques for the directed evolution experiments of enzymes, with the possibility to test millions or billions of variants to be tested at each cycle. In this project, I will introduce the use of full-gene next generation sequencing to supervise the exploration of variants at the sequence level and quantitatively characterize the fitness landscape, with a focus on non-additive effects of mutations into fitness (epistasis). Furthermore, this information will be included in DE protocols to guide a more efficient exploration of the sequence space.
The project is a strongly interdisciplinary project consisting of experimental synthetic biology, physics modelling and bioinformatics analysis. It is focused in the study of DNA processing enzymes such as polymerase and endonucleases. The proposal includes the development of specific tools which should have an immediate impact on the scientific community: i. extend the applications of next generation sequencers to characterize full length genetic libraries of protein variants ; ii. adapt quantitative methods, previously developed for sets of structurally homologous proteins and derived from Potts model to study the catalytic properties of during directed evolution. iii. develop a new experimental protocol to control the number of mutations in libraries.
The analysis will provide a better understanding of the topology of the fitness landscape of an enzyme, and its distortions under selective pressures, thereby clarifying the relations between sequence,function and evolution in proteins.
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 mathematics pure mathematics topology
- natural sciences biological sciences genetics mutation
- natural sciences chemical sciences catalysis
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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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-EF-ST - Standard EF
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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.
75231 Paris
France
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.