Project description
Molecular insight into Mycobacterium tuberculosis
Tuberculosis (TB) remains a significant cause of global mortality, and many molecular aspects of its pathogenesis remain elusive. A key factor in the virulence of Mycobacterium tuberculosis is the surface protein heparin-binding haemagglutinin adhesin (HBHA), which binds to various host glycan structures and mediates cell adhesion. The EU-funded HADES project will employ nuclear magnetic resonance to further elucidate the structure and mechanism of action of HBHA at different phases of the life cycle of Mycobacterium tuberculosis. Given the role of HBHA in TB dissemination, diagnosis and therapy, the project's findings are of great clinical significance.
Objective
Tuberculosis (TB) is one of the most aberrant causes of global mortality and the molecular mechanisms of its pathogenesis are not well understood. The extrapulmonary dissemination of TB involves requires a crucial virulence factor designated as heparin-binding haemaglutinin adhesin (HBHA). HBHA is a 28 kDa dimeric protein localised at the surface of the Mycobacterium tuberculosis (MTB) that binds dextran sulphate, dermatan sulphate, glycosaminoglycans and heparan-sulphate proteoglycans thus mediating the adhesion with epithelial cells and to extracellular matrix components. Despite a crucial role in the dissemination of TB, a key relevance as strong diagnostic antigen and as therapeutic target, there is currently limited understanding of the structure and mechanism of action of HBHA.
The ambitious aim of this proposal is to characterise at high-resolution the mechanisms of function of HBHA in different phases of the life cycle of MTB. To achieve this ambitious target, we will carry out an integrated investigation of solution-state and solid-state NMR nuclear magnetic resonance (NMR) to acquire high-resolution data on the interaction of HBHA with membranes of MTB.
The NMR experiments will be complemented with biophysical studies and mutagenesis to accurately define the relationship between structure, dynamics and function of HBHA.
Our preliminary data suggest that this ambitious project comes at the most opportune time as we now have tools, materials and knowledge to resolve this important goal for biochemistry and reveal the propeties of a crucial molecule for the mechanism of extrapulmonary dissemination of TB.
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.
- social sciences sociology demography mortality
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences clinical medicine pneumology tuberculosis
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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-2019
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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.
80138 Napoli
Italy
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.