Objective
Cellular respiration provides energy to power essential processes of life. Respiratory complexes are macromolecular batteries coupling electron flow through a wire of metal clusters and cofactors with proton transfer across the inner membrane of mitochondria and bacteria. Waste products of these cellular factories are reactive oxygen species causing ageing and diseases. Assembly and maturation mechanisms of respiratory complexes remain enigmatic because of their membrane location, multisubunit composition and cofactor insertion. E. coli Complex I, one of the largest membrane proteins, composed of 14 conserved subunits with 9 Fe/S clusters and a flavin, is a minimal model for its 45-subunit human homologue. When proton pumping by respiratory complexes is affected, bacteria become resistant to antibiotics requiring proton gradient for uptake. Based on the latest genetic data, we realize that the huge E. coli macromolecular cage, the structure of which we recently solved by cryo-electron microscopy (cryoEM), in conjunction with a novel protein cofactor, is a specific chaperone for Fe/S cluster biogenesis and assembly of respiratory complexes. This integrated multidisciplinary project combines cryoEM and other structural, biophysical and spectroscopic techniques, to uncover the functional mechanism of this emerging chaperone. The structural plasticity of the chaperone fuelled by ATP hydrolysis, and its interaction with Fe/S cluster biogenesis systems and the main respiratory complexes as a function of stresses, will be scrutinized to gain quasiatomic insights into the way the chaperone operates on its substrates. A novel technology for synergetic in situ investigation of protein complexes in the bacterial cytoplasm by optical imaging, state-of-the-art cryogenic correlative light and electron microscopy, and subtomogram analysis, will be developed and used to obtain snapshots of the chaperone-substrate interactions in the cellular context.
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
- natural sciences physical sciences optics microscopy super resolution microscopy
- natural sciences physical sciences optics microscopy electron microscopy
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
- natural sciences biological sciences molecular biology structural biology
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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.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
MAIN PROGRAMME
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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.
ERC-COG - Consolidator Grant
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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) ERC-2014-CoG
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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.
75794 PARIS
France
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.