Project description
Evolution of antibiotic resistance enzymes in bacteria
Antibiotic resistance represents one of the biggest public health challenges of our time. The emergence of resistant bacteria interferes with the activity of existing antibiotics and severely disrupts routine procedures and hospitalisation. The EU-funded PROBYDE project is working under the hypothesis that evolution of antibiotic resistance is a consequence of repeatable genetic changes. Researchers will conduct directed evolution experiments to understand the determinants of this repeatability. The work will focus on enzymes implicated in drug resistance and provide fundamental information on how mutations force key molecules to follow specific adaptive paths.
Objective
The fast evolution of bacterial pathogens towards antibiotic resistance is estimated by 2050 to be killing 10 million people every year. Consequently, much interest is being directed towards finding ways to curb or even arrest this evolutionary process. Of note, sequencing efforts are revealing that many of the genetic changes that drive resistance evolution are often repeatable. Understanding what drives this repeatability is of foremost importance if we ever want to develop interventions aimed at anticipating and preventing the evolution of undesirable variants. Here, I will aim at advancing our understanding of evolutionary repeatability in several clinically-relevant, drug-resistance enzymes spanning a range of GC compositions. I will use this relevant model system to empirically test recent predictions on the roles of mutation bias and GC content in shaping mutational pathways. To this end, I will conduct high-throughput 'in vitro' Directed Evolution experiments to explore the potential adaptive paths available via single step mutations among the drug-resistance enzymes. Next, I will compare these 'in vitro' predictions with the outcomes of highly-parallel antibiotic adaptation experiments conducted with bacterial strains with strong mutation biases (e.g. mutators) carrying the same panel of enzymes. By producing important insights into some of the key determinants of evolutionary repeatability, PROBYDE aspires to form a knowledge base that may help harness evolution not only in bacterial pathogens, but also in other human-relevant systems such as cancer, crop pests and industrial microbes.
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 evolutionary biology
- natural sciences biological sciences genetics mutation
- agricultural sciences agriculture, forestry, and fisheries agriculture
- medical and health sciences basic medicine pharmacology and pharmacy drug resistance antibiotic resistance
- 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.1.3. - 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.
28040 MADRID
Spain
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.