Objective
The human proteome is primarily synthesized at the endoplasmic reticulum (ER) membrane through the ribosome-translocon complex. This assembly is crucial for protein synthesis, translocation, membrane insertion and post-translational modification. Depending on the type of protein being synthesized, the translocon adopts either a secretory (soluble proteins) or multipass (membrane proteins) form. Newly synthesized proteins often carry a signal peptide that is cleaved by the signal peptidase complex (SPC) co-translationally, indicating possible structural interactions between the ribosome-translocon complex and the SPC during this process. In the proposed project, I aim to elucidate these interactions and explore how different translocon variant recruitment affects polysome topology, as well as reveal the structural interactions between the ribosome-translocon complex and the SPC during signal-peptide cleavage in high-resolution. I will carry out the project in three phases. First, I will develop a multimodal mRNA probe to detect ribosome-translocon-SPC complexes, enabling their visualization during protein synthesis. In the second phase I will investigate how different translocon variants affect polysome topology using advanced imaging techniques such as cryo-correlative light electron microscopy (cryo-CLEM) and cryo-electron tomography (cryo-ET) ex vivo. These methods will help identify how polysome topology is affected by recruitment of specific translocon variants interact at the ER membrane. Finally, I will use single-particle cryo-electron microscopy (SPA cryo-EM) to achieve a high-resolution reconstruction of the ribosome-translocon-SPC complex, providing detailed insights into the molecular interactions during nascent polypeptide synthesis and signal peptide cleavage. This research outcomes of the proposed project will significantly advance our understanding of ER protein biogenesis and its regulatory mechanisms.
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 biochemistry biomolecules proteins proteomics
- natural sciences mathematics pure mathematics topology
- 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.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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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) HORIZON-MSCA-2024-PF-01
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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.
3584 CS Utrecht
Netherlands
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.