Project description
The pathogen genetics behind the clinical forms of leprosy
Leprosy is caused by Mycobacterium leprae and Mycobacterium lepromatosis, which are difficult to study as they cannot be cultivated in the laboratory. The recent sequencing of different bacterial isolates has identified hypermutated genes with potential roles in drug resistance and species adaptation. The scope of the EU-funded LEPVORS project is to associate these genetic changes with clinical phenotype and drug resistance. Moreover, using recent molecular advances such as next generation sequencing, researchers will study additional strains isolated from rarer clinical forms of leprosy. Results will provide unprecedented insight into the biology and host adaptation of the causative agent of leprosy.
Objective
Leprosy is a multiform infection caused by Mycobacterium leprae, an uncultivable bacLeprosy is a slow and chronic infection caused by Mycobacterium leprae. Recent advances in the next generation sequencing offer a new possibility to study the physiopathology of M. leprae, an uncultivable bacteria on anexic media. In 2018, the comparative analysis of 154 M. leprae genomes from 25 countries identified three hypermutated genes including two (ribD and fadD9) probably associated with drug-resistant and the most mutated one being ml0411 with a potential role in host adaptation. In a mycobacterial species, like M. leprae, with such a reduced number of coding genes, it is reasonable to assume that this high rate of mutations probably led to the modification of essential biological functions. In addition, the recent development of more efficient molecular tools can now help to obtain the whole genome sequencing of the strain from the low representative forms of the disease. This could help to identify more of these highly mutated genes and establish a link between the pathogen genetic and the clinical disease outcome. This project proposes to functionally characterize some of the mutations identified but also to identify new candidates which could be linked with differences in host phenotype. The study has three specific aims: Specific aim 1 will focus on potential new genes involved in M. leprae drug resistance. Using surrogate mycobacteria such as M. tuberculosis and M. haemophilum, we will test the drug susceptibility of mutated strains in fadD9 and ribD compared to wild-type strains. In specific aim 2, we will investigate the role of ml0411 and mutated version on the host innate immune response modulation In specific aim 3, we will focus on the whole genome sequencing of M. leprae strain from the less represented clinical form of leprosy, the tuberculoid pole to identify new genetic differences in the bacteria which could be associated with different host phenotypes.
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 bacteriology
- medical and health sciences basic medicine immunology
- medical and health sciences basic medicine pharmacology and pharmacy drug resistance
- natural sciences biological sciences genetics mutation
- natural sciences biological sciences genetics genomes
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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.1.3. - 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-GF - Global Fellowships
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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-2018
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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.
4123 ALLSCHWIL
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.