Objective
Structure determination of dynamic macromolecular molecular machines and elucidating their conformational landscapes are fundamental tasks of structural biology. The ribosome as a paradigmatic macromolecular machine interacts with numerous ligands and factors throughout its functional cycles, which in turn are driven and regulated by various conformational modes. Project DeepRibosome proposes a new way to perform structural studies. It is based on our recent finding that E. coli ex-vivo derived polysomes carrying the translatome can be efficiently reactivated in the PURE in vitro translation system. Cryo-EM of actively translating ribosomes results in comprehensive structural landscapes. During steady state, all intermediates are expected to be present, including the short-lived ones. Supported by preliminary data, we estimate that applying multi-particle sorting of images we can resolve states with a lifetime in the one-digit millisecond range. This allows us to study under optimal conditions fast steps such as the GTPase factor-dependent reactions or peptidyl-transfer/accommodation without artificially stalling the reaction by antibiotics or non-cleavable GTP analogues. The structural studies will be accompanied by functional assays including Ribo-seq to monitor translation of the cell-derived translatome in a cell-free system. While, we will also conduct in situ structural analysis for comparison, the strength of our new approach is that we can track translation from an integrated structural and functional perspective, preserving/reconstituting many native features but under defined and controllable conditions. This will not only provide insights into the molecular mechanism of translation at the next level of understanding but also allow us to answer long-standing questions e.g. how exactly the physicochemical environment (temperature, ions) or auxiliary factors impact translation. It will also provide new means to study the inhibition mechanisms of antibiotics.
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 physical sciences optics microscopy
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs antibiotics
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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 - HORIZON ERC 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-2024-ADG
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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.
10117 Berlin
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.