Project description
Time-resolved initiation and progression of mitochondrial protein synthesis
Mitochondria power virtually every process in the human body via adenosine triphosphate, the cell’s energy ‘currency’. They have their own DNA and manufacture proteins on dedicated mitochondrial ribosomes. Defects in this machinery cause severe mitochondrial disorders and contribute to drug toxicity. The precise sequence of molecular events underlying mitochondrial protein synthesis, including initiation and elongation (addition of amino acids one by one), remains poorly understood. With the support of the Marie Skłodowska-Curie Actions programme, the DYNAMITE project aims to capture this dynamic process in unprecedented detail by combining rapid kinetic measurements with time-resolved cryo-electron microscopy. The resulting first-ever dynamic framework of human mitochondrial translation could lead to understanding of and therapies for mitochondrial disorders.
Objective
The DYNAMITE project aims to uncover the precise sequence of molecular events that govern human mitochondrial translation initiation and its transition to elongation. Mitochondria are essential for energy production, and defects in their translation machinery cause severe diseases and contribute to drug toxicity. Despite recent structural advances, the dynamic steps of initiation remain poorly understood.
To address this gap, DYNAMITE will combine kinetic assays using stopped-flow fluorescence to quantify the timing and order of initiation events with time-resolved cryo-electron microscopy to capture structural snapshots of transient intermediates during initiation and early elongation. These datasets will be integrated into a unified, time-stamped mechanistic model, linking reaction rates with structural transitions.
This work will deliver the first dynamic framework of human mitochondrial translation, providing fundamental insight into how the mitoribosome functions at its earliest stages. By revealing regulatory checkpoints and structural transitions, DYNAMITE will open new avenues for studying disease-associated mutations and designing safer, mitochondria-sparing drugs. Ultimately, this knowledge could help reduce the risk of mitochondrial toxicity, which is a major cause of late-stage drug failure, and accelerate the development of effective therapies for mitochondrial disorders and other conditions linked to mitochondrial dysfunction.
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.
This project's classification has been human-validated.
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.
This project's classification has been human-validated.
- medical and health sciences basic medicine pharmacology and pharmacy drug safety
- natural sciences biological sciences genetics
- natural sciences biological sciences cell biology
- medical and health sciences basic medicine pathology
- natural sciences biological sciences molecular biology structural biology
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-2025-PF
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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.
171 77 STOCKHOLM
Sweden
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.