Objective
Fidelity during information transfer is essential for life, but it pays to be unfaithful if it provides an evolutionary advantage. The immune system continuously generates diversity to put up with recurrent pathogen challenges, and many viruses, in its turn, have evolved mechanisms to generate diversity to evade immune restrictions, even at the cost of enduring high mutation rates.
Synonymous codons are not used at random and are not translated with similar efficiency. A large proportion of viruses infecting humans, especially those causing chronic infections, display a poor adaptation to the codon usage preferences of their host. This observation is a paradox, as viral genes completely depend upon the cellular translation machinery for protein synthesis. The poor match between codon usage preferences of virus and host negatively affects speed and accuracy of viral protein translation. We propose here that maladaptation of codon usage preferences in human viruses may have an adaptive value as it decreases translational fidelity, results in the synthesis of an ill-defined population of viral proteins and provides a way to escape immune surveillance.
We will address the fitness effects of codon usage bias at the molecular and cellular levels, and later at the organism level in a rabbit model of papillomavirus infection. We will apply experimental evolution to analyse genotypic changes by means of next generation sequencing and will monitor phenotypic changes through real-time cell monitoring techniques, comparative proteomics, and anatomopathological analysis of virus-induced lesions.
Our results will help solve the evolutionary puzzle of codon usage bias, and will have implications for the development of therapeutic vaccines to guide the immune response towards the identification and targeting of the main protein species, avoiding the chemical noise generated by protein mistranslation.
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
- medical and health sciences basic medicine immunology
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs vaccines
- medical and health sciences clinical medicine oncology cervical cancer
- medical and health sciences health sciences infectious diseases viral diseases DNA viruses
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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.1.1. - 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-2014-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.
75794 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.