Objective
Complex I (NADH:ubiquinone oxidoreductase), one of the largest membrane-bound enzymes in the mammalian cell, uses the reducing potential of NADH to drive protons across the inner mitochondrial membrane and power ATP synthesis. It is a keystone of metabolism, crucial for survival of human cells, and a primary site of mitochondrial dysfunctions and clinical disease. Complex I is also an efficient energy-converting biomachine, which shares conserved subunits, a molecular architecture, and modular design with prokaryotic type-4 hydrogenases, such as formate hydrogenlyase (FHL), that contribute to microbial H2 metabolism and geochemical cycles. Detailed cryo-electron microscopy (cryoEM) structures have defined the physical framework of the catalytic machinery in complex I, but there are wide knowledge gaps in central aspects of how it works, and no firm foundation of functional data to distinguish competing mechanistic proposals. ModularBioMachine will combine advanced strategies for structure, nanoassembly, function and genetics to transform knowledge of the reversible energy-transducing mechanism of complex I and FHL, exploiting their similarities and differences for enhanced insights and impact. It will exploit two powerful complex I platforms, complex I-containing proteoliposomes, which enable cryoEM under precisely defined conditions during energy-linked catalysis, and complex I from Paracoccus denitrificans, which combines cryoEM, genetics and advanced functional analyses in a single system – and extend both to study FHL. Focussing on three crucial knowledge gaps, the power stroke at the heart of energy conversion, the clockwork mechanism that defines the moving parts, and the proton wiring diagrams, ModularBioMachine will deliver a coherent, integrated understanding of the shared engineering principles and molecular mechanism of energy conversion in these evolutionary-linked biomachines at an intersection of the mitochondrial and microbial worlds.
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 physical sciences optics microscopy
- medical and health sciences basic medicine neurology stroke
- natural sciences chemical sciences catalysis
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
You need to log in or register to use this function
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.
-
HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
See all projects funded under this programme
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.
HORIZON-ERC - HORIZON ERC Grants
See all projects funded under this funding scheme
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-2024-ADG
See all projects funded under this callHost institution
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.
CB2 1TN CAMBRIDGE
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.