Objective
Living cells are constantly barraged by perturbations that originate within themselves. Especially abundant – far more than DNA mutations – are two kinds of such perturbations. The first is gene expression noise, pervasive stochastic variation of transcript and protein levels. The second is mistranslation noise, the misincorporation of amino acids by ribosomes during protein synthesis. Organisms and protein molecules can evolve robustness – the persistence of well-adapted phenotypes – to both kinds of noise. Theory predicts that noise and robustness can affect the adaptive evolution of new proteins, but we do not know whether they help or hinder adaptive evolution. We hypothesize that noise and robustness can accelerate protein evolution both separately and jointly. To validate this hypothesis, we will evolve light-emitting fluorescent proteins towards new color phenotypes via directed laboratory evolution in E.coli. During evolution, we will manipulate expression noise by driving FP expression from noisy or quiet promoters, and we will manipulate mistranslation via host strains with low and high mistranslation rates. We will manipulate protein robustness in three biologically important ways, chaperone overexpression, gene duplication, and stabilizing selection. We will study how fast FPs evolve new colors, and analyze protein evolutionary dynamics through a combination of high-throughput sequencing, engineering of selected adaptive mutations, and data-driven modeling. Our project will show how a ubiquitous but poorly understood source of phenotypic variation affects protein innovation. It will also help engineers discover new protein functions. Moreover, our work will help establish FPs as a major platform to study protein evolutionary dynamics. By revealing noise as a new and crucial factor in protein evolution, our observations have the potential to revolutionize molecular evolution research, much like earlier studies of noise have revolutionized cell biology.
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 biochemistry biomolecules proteins
- natural sciences biological sciences evolutionary biology
- natural sciences biological sciences genetics mutation
- natural sciences chemical sciences organic chemistry amines
- natural sciences biological sciences molecular biology molecular evolution
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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-ADG - Advanced 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-ADG
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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.
8006 Zurich
Switzerland
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.