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Structural studies of the human mitochondrial RNA life cycle

Project description

Unravelling mitochondrial gene expression

Mitochondria, the energy powerhouses of the cell, contain their own DNA. Mitochondrial DNA uses unique mechanisms for transcription and translation. Despite the fact that cellular respiration depends on mitochondrial gene expression, important processes like the RNA life cycle are still poorly understood. The goal of the ERC-funded MitoRNA project is to address these gaps in knowledge and investigate how the different steps in mitochondrial gene expression are functionally coupled. Researchers will follow a structural biology approach to define the molecular basis of mitochondrial RNA metabolism. Results will advance our understanding of mitochondrial gene expression and fundamental mitochondrial biology.

Objective

Mitochondria maintain an organellar genome that encodes for subunits of the respiratory chain. Its coordinated expression is essential for eukaryotic life, and defects in this process lead to severe disease in humans. Mitochondrial gene expression is carried out by unique dedicated molecular machineries, but the underlying molecular mechanisms remain poorly characterized. During my previous work as a PhD student and Project Leader, I provided the structural basis of human mitochondrial transcription. At the same time, structural insights on mitochondrial translation were reported. However, our understanding of mitochondrial gene expression remains limited due to two fundamental knowledge gaps. First, we lack a molecular understanding of the complex mitochondrial RNA life cycle that takes place in between transcription and translation. Second, we do not know how the different steps of mitochondrial gene expression are functionally coupled, as they are not separated by membranes. With MitoRNA, we propose to take the next big leap towards a mechanistic understanding of mitochondrial gene expression by addressing these blind spots. Using an innovative integrated structural biology approach, we will define the molecular basis of the human mitochondrial RNA life cycle and how it is embedded in the concert of mitochondrial gene expression. In particular, we will investigate the structural basis of various key steps of mitochondrial RNA metabolism in vitro and in situ, and dissect how they are coupled to each other. This ground-breaking work will open up the next frontier in mitochondrial biology by drawing a molecular picture of human mitochondrial RNA metabolism and providing insights into the functional organization of mitochondrial gene expression. In addition, it will also advance methods to study mitochondrial biology from the atomic to the organellar scale.

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Topic(s)

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2023-STG

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Host institution

UNIVERSITAETSMEDIZIN GOETTINGEN - GEORG-AUGUST-UNIVERSITAET GOETTINGEN - STIFTUNG OEFFENTLICHEN RECHTS
Net EU contribution

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.

€ 1 499 754,00
Address
Robert-Koch-Strasse 40
37075 Goettingen
Germany

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Region
Niedersachsen Braunschweig Göttingen
Activity type
Higher or Secondary Education Establishments
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Total cost

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.

€ 1 499 754,00

Beneficiaries (1)

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