Objective
The macrocyclic lactones such as ivermectin are the cornerstone for the treatment of key nematode infections of livestock, crops and man. Resistance to many of these broad-spectrum anthelmintics is becoming commonplace, while new classes of active compounds are increasingly difficult to find, threatening food supplies and public heatlh worldwide. The exact molecular and biochemical mechanisms of resistance, particularly to the widely used macrocyclic lactone class, are still poorly understood, impeding the development of efficient strategies to control drug resistance. I hypothesize that the amphidial sensory organs of nematodes are the major route of macrocyclic lactone drug uptake and that mutations in this uptake mechanism represents the primary source of drug resistance. In the first phase of the project, I will develop laboratory methods for testing amphid function in two parasitic nematodes of veterinary significance, the trichostrongyles Haemonchus contortus and Teladorsagia circumcincta. These techniques will be applied on drug resistant and sensitive isolates to evaluate the role of amphids in ivermectin uptake. In the second phase, I will use the C. elegans model to generate mutants resistant to three major classes of anthelmintic drugs, ivermectin, the benzimidazole albendazole and the imidazothiazole levamisole. I will then apply genomic tools to identify alleles responsible of this multi-drug resistance phenotype. This project aims to understand the link between amphid defects, anthelmintic drug uptake, and development of resistance, and will generate a thorough knowledge of this unexplored and apparently widespread resistance mechanism in nematodes. These results will also pave the way to the implementation of a fast and reliable measurement of drug resistance in the field. On the whole, the project will bring a direct contribution to current veterinary and public health challenges by suggesting new strategies to limit the emergence of drug resistance.
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.
- medical and health sciences health sciences public health
- natural sciences biological sciences genetics mutation
- agricultural sciences agriculture, forestry, and fisheries agriculture
- agricultural sciences animal and dairy science domestic animals animal husbandry
- medical and health sciences basic medicine pharmacology and pharmacy drug resistance multidrug resistance
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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-2016
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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.
G12 8QQ Glasgow
United Kingdom
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.