Project description
Research sheds light on how proteins are made and used
Understanding the role of protein translation in eukaryotic cells is crucial, as it directly impacts organelle function and cellular architecture. The ERC-funded 3DTOP project will address this by uncovering the intricate connections between protein synthesis and organelle biogenesis. By combining cutting-edge functional genomics with cryogenic electron tomography, researchers will seek to map where protein translation occurs near organelles. Through high-throughput imaging, they will determine where mRNAs are located and how ribosomes, the protein builders, are arranged. The study will investigate how this local translation adapts to different conditions and affects organelle functions. Researchers aspire to redefine existing perceptions of protein synthesis, revealing a complex network of translation locales that regulate cell structure and operations.
Objective
In eukaryotic cells, many proteins are produced next to the organelles where they function, demonstrating a link between translation and protein targeting. The mechanisms of this connection are mostly unknown. In this proposal, I bring together the fields of translation regulation and organelle biogenesis to find this out.
I approach the problem with a powerful combination of functional genomics and cryogenic electron tomography (cryo-ET). First, I want to create a quantitative map of proximal translation next to all the organelles and their sub-domains. Using high-throughput imaging, I will determine localizations of all the mRNAs and their dependence on translation. I will also map the positions and orientations of ribosomes next to all the membranes using proximity labelling and direct quantification of native ribosomes with cryo-ET. Beyond mapping, I want to understand how this local translation map is adapted to different conditions. Using high-throughput screening, I will determine what global and local factors establish and regulate proximal translation at each organelle. Finally, I will investigate the role proximal translation plays in essential organelle functions and get mechanistic insights into how local regulators help to carry it out.
When completed, the project will overturn the binary view of either Sec61-coupled translation on the ER surface vs. free cytosolic translation of all the other organellar proteins. Instead, I will uncover a holistic picture of multiple proximal translation locales with distinct regulation. I aim to discover new connections between the two fundamental processes of protein synthesis and organelle biogenesis and thus make a ground-breaking advance in the understanding of how cells coordinate their architecture and functions.
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 genetics
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences physical sciences optics microscopy electron microscopy
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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)
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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
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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
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2024-STG
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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.
67663 Kaiserslautern
Germany
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