Project description
Evolution to the rescue: the paradigm of genome maintenance
Faithful DNA replication is vital for maintaining genome and cell integrity. However, various exogenous and endogenous factors can cause replicative stress and lead to cancer and developmental defects. The working hypothesis of the EU-funded GENMAINEVO project is that cells respond to replicative stress through the acquisition of mutations that help them adapt their fitness. Researchers will employ the budding yeast Saccharomyces cerevisiae as a model organism to study, through directed evolution, how cells respond to perturbations in genome maintenance at the genome and biology levels. Results will provide important knowledge on evolutionary mechanisms and how they can rescue key cellular processes such as genome maintenance.
Objective
Genome maintenance describes a subset of conserved cellular processes responsible for the faithful propagation of genomes across cell divisions. Defects in genome maintenance have been associated with several medical disorders such as cancer, aging and developmental defects. Recently we showed how perturbations in DNA replication, one of the most conserved processes in genome maintenance, induce an evolutionary process that leads to the sequential and concerted accumulation of adaptive mutations that increase the cellular fitness in response to replication stress. To what extent this fast-evolutionary rescue applies to other defects in genome maintenance, and what evolutionary trajectories are responsible for adaptation under different cellular stresses remain unexplored questions. Furthermore, while adaptive mutations rewire genetic networks to achieve increased fitness, their pleiotropic effect on cell biology is unknown. Here I propose a plan to comprehensively investigate these questions by taking advantage of a multi-disciplinary methodology using the budding yeast S. cerevisiae as a eukaryotic model organism. Experimental evolution of cells perturbed in several aspects of genome maintenance will be combined with computational and quantitative approaches to study their evolutionary adaptation in response to the different initial perturbations. Molecular genetics and cell biology techniques will be then used to investigate the consequence of these adaptations to cell’s sensitivity to genotoxic agents, a phenotype directly relevant for the treatment of medical-relevant diseases including cancer and infection diseases. The knowledge generated by the proposed research project will reveal important aspects of how cells adapt to genetic perturbations, with implications for both medical therapies and evolutionary cell biology at large.
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 molecular biology molecular genetics
- natural sciences biological sciences evolutionary biology
- natural sciences biological sciences cell biology
- natural sciences biological sciences genetics mutation
- 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.1.3. - 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 - Marie Skłodowska-Curie Individual Fellowships (IF)
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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-2020
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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.
1067-001 LISBOA
Portugal
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.