Project description
How life’s protein machines assemble
Inside each cell, proteins are found in complex patterns, sustaining the functions of the body. However, how exactly these complex patterns are achieved so accurately is a puzzle. Recent findings suggest the assembly of many proteins, even as they are synthesised by the cell’s ribosome, defying traditional textbook explanations. The ERC-funded CoTransComplex project aims to develop a new approach, ranging from ribosome profiling and single-molecule imaging to cryo-electron microscopy. The goal is to examine this phenomenon to a degree never previously achieved. The findings could change how diseases resulting from problematic protein assembly are understood, providing a breakthrough in biotechnology and medicine.
Objective
Most proteins function within larger complexes. How these intricate structures are correctly formed is poorly understood, yet critical to all cellular processes and pathological conditions. Recent breakthroughs suggest that multi-protein complexes form co-translationally, by super-assemblies of multiple ribosomes and other cofactors that are coordinated in time and space. This striking notion contrasts starkly with textbook models and is key to the possibilities and failures of complex formation. However, owing to technical limitations, the mechanisms and scope of actively coordinated protein assembly are poorly understood.
Elucidating how these large and transient co-translational formations produce protein complexes throughout the genome is a next-level challenge that cannot be addressed by a single discipline. We propose a unique merging of cutting-edge approaches: 1) Ribosomal profiling to detect interactions between ribosomes engaged in assembly and cofactors genome-wide, 2) Single-molecule force spectroscopy and super-resolution imaging to reveal ribosome movements and nascent chain assembly. 3) Cryo-EM and tomography to elucidate the structural basis of ribosome interactions that enable direct assembly.
Our program addresses 1) the coordination of multiple ribosomes in time and space, 2) the folding and assembly of nascent chains, and guidance by chaperones and novel cofactors, 3) the major protein complexes classes of homo-dimers, higher-order oligomers, hetero-dimers, and complexes formed at membranes. This ambitious program will provide insight of unprecedented detail and scope, spanning from the cellular to the atomic level, from in vivo to in vitro, from genome-wide patterns to molecular mechanisms, and from bacteria to human cells. It will impact a vast spectrum of protein complexes, reveal unknown layers of control in protein biogenesis, with implications for ribosome quality control, artificial protein design, and mechanisms of disease.
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 biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences genetics genomes
- natural sciences physical sciences optics spectroscopy
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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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HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
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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-SYG - HORIZON ERC Synergy Grants
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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-2022-SYG
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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.
69117 Heidelberg
Germany
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