Objective
The mechanism of protein translation by ribosomes has been the focus of recent single molecule investigations. Understanding translation at a single-molecule level is of particular interest to the life sciences and relevant for various degenerative diseases. Although protein translation and folding are well studied subjects, cotranslational folding has been proven difficult to observe. How proteins adopt their native structure with efficient fidelity while being synthesized by the ribosome remains largely unexplored. Using optical tweezers we recently measured the mechanics of synthesis and simultaneous folding in real-time, in the absence of chaperones. We found that cotranslational folding occurs at predictable sequence locations, exerting forces on the nascent polypeptide chain. We showed that transient pauses of translation occur in particular locations along the protein sequence, facilitating native secondary structure formation. Several crucial mechanistic questions concerning the effects of chaperones on co-translational folding remain unanswered: How do the chaperones trigger factor (TF), the major bacterial heat shock protein 70 (Hsp70/DnaK) and the GroEL/ES chaperonin system affect cotranslational protein folding? Do they affect the translation rate? What effect do the chaperones have on initial hydrophobic collapse? When and how often do they (un)bind? How do these chaperones assure reliable and fast native folding during protein synthesis? Here, I propose a combined optical tweezers and laser scanning confocal microscopy study to investigate the effects of chaperones on cotranslational folding in real-time, using the host's instruments, chaperones and collaboration network, as well as my previously developed cotranslational assay and collaboration network. The group of Prof. S. J. Tans at AMOLF with its expertise and experience in single-molecule chaperone investigations is ideally suited for me to pursue this study of cotranslational chaperone activity.
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 protein folding
- natural sciences physical sciences optics microscopy confocal microscopy
- natural sciences biological sciences genetics genomes
- natural sciences physical sciences optics laser physics
- natural sciences physical sciences optics spectroscopy
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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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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
MSCA-IF-EF-ST - Standard EF
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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) H2020-MSCA-IF-2016
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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.
3526 KV 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.