Project description
Experiments and models to reveal mechanisms of translation regulation with near-atomic detail
Protein synthesis, during which the sequence of nucleotides in mRNAs is translated to a sequence of amino acids, is catalysed by the millions of ribosomes in a human cell. The ribosomes are regulated by a plethora of proteins. The composition of these regulatory complexes, their functions, distribution, and how they change in response to cellular stress are largely unknown. The ERC-funded TransFORM project aims to address these gaps with new technologies, including cryo-electron tomography, crosslinking mass spectrometry and integrative structural modelling. In systems spanning from single human cells to organoids, the team plans to reveal the structure and composition of translation complexes and regulatory mechanisms across cellular space in adaptation to stressors and viral infection.
Objective
Translation – the fundamental process of protein synthesis catalyzed by ribosomes - has been extensively characterized from a biochemical, structural, and mechanistic perspective. However, how exactly the translation machinery operates as an interconnected system of millions of ribosomes in cells is poorly understood. Within the cell, ribosomes associate with a multitude of regulatory proteins forming a variety of specialized complexes and distributing across cellular space in a manner that depends on cell state. What is the specific composition of those complexes, their significance, and their functional role? How are they defined and regulated by subcellular compartmentalization? How do they change in response to cellular stress? Our TransFORM synergy team brings together experts in method development for in-cell structural biology and the biology of translation to allow us for the first time to attack these fundamental problems. Building on our prior achievements, we aim to synergistically develop novel methods of cryo-electron tomography with imaging across scales in conjunction with crosslinking mass spectrometry and integrative structural modeling for near-atomic structure determination directly in cells. TransFORM will determine the ribosome structural and functional states across the translation cycle in human cells, following distinct 40S, 80S, and disomal particles (80S+80S), in and out of polysomes and across different protein synthesis regimes. We will uncover structural and compositional changes and regulatory mechanisms across cellular space, in adaptation to perturbations by stressors and during viral infection. Our model systems will span from single cells to organoids. TransFORM will provide a detailed and comprehensive in-cell map of the essential process of protein synthesis while delivering innovative methods for the next-generation of in-cell structural biology.
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.
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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)
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-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-2023-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
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.