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Content archived on 2024-06-18

Dissecting a minimal genome: a physical investigation of DNA transactions in mitochondria

Objective

I propose to unravel parts of the mechanochemistry of two key genome transactions: replication and transcription using an array of single-molecule techniques. To this end, I propose to study the minimal genomic machinery of mitochondria. Mitochondria are organelles in eukaryotic cells that contain their own DNA (mtDNA). Significant understanding of the biochemistry of DNA transactions in mitochondria is obtained from the in vitro reconstitution of mitochondrial replication and transcription. However, elucidating the physics of these molecular mechanisms has only just started. A major challenge of the coming decades will be dissecting and quantifying biological systems to such an extent that it makes predictive modeling possible. Single-molecule tools play a major role in this development. Hence, I plan within the scope of this proposal, to combine optical manipulation with powerful fluorescent techniques. This combination of single-molecule manipulation and fluorescence has much more potential than has been explored, so far. With the development of such tools complex biological systems can not only be controlled and measured but also visualized at the same time. The human mitochondrial genetic machinery is an ideal system for such an approach, because replication and transcription can be re-created in vitro with only seven proteins. Hence, this proposal represents a unique opportunity to quantitatively dissect a genetic machine that is actually accessible by biophysical tools. Finally, about 1 in 5000 humans suffers from a disease caused by mutations of in the mtDNA. The research proposed here will permit direct observation of proteins in action. Normal and dysfunctional proteins can thus be compared, permitting insight in the mechanistic basis of a disorder.

Fields of science (EuroSciVoc)

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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.

Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

ERC-2010-StG_20091118
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Funding Scheme

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ERC-SG - ERC Starting Grant

Host institution

STICHTING VU
EU contribution
€ 1 497 868,00
Address
DE BOELELAAN 1105
1081 HV Amsterdam
Netherlands

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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.

No data

Beneficiaries (2)

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