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Tracking conformational dynamics of cohesin with MINFLUX

Project description

Unveiling the role of cohesin in DNA compaction

Diploid eukaryotic cells contain approximately 6 billion base pairs of DNA that stretch over 2 m in length. To fit into the nucleus, DNA associates with histone proteins and gets compressed into chromatin fibres, yet it manages to undergo replication and transcription. The EU-funded mcMINFLUX project is interested to understand the role of the protein cohesin, conventionally known to keep sister chromatids together, in DNA compaction. To study cohesin dynamics, researchers will employ the MINFLUX nanoscopy method that can provide nanometre resolution in living cells. Results will advance our knowledge on DNA condensation, replication and transcription.

Objective

The DNA contained in each of our cells has a size of about 2 m and is fitted into the nucleus which is about six orders of magnitude smaller. It is unclear, how this extraordinary compaction is achieved and how the cell can still carry out highly regulated processes like gene expression, DNA replication, and DNA repair in such a dense environment.
Cohesin is a protein that has been shown to play an important part in DNA compaction, especially in sister-chromatid cohesion. Recently, it has been observed that cohesin extrudes loops of DNA to achieve compaction, but how exactly it carries out its function is unknown.
Fluorescence spectroscopy is a powerful tool to investigate conformational dynamics of biomolecules. MINFLUX is a recently developed method which localizes single molecules with a precision of a few nanometers. Here, I propose a new method based on MINFLUX which will allow to track fluorescent labels on large bio-molecular complexes with nanometer spatial and millisecond time resolution. The method will be used to study conformational dynamics of cohesin in vitro and investigate the mechanism of loop extrusion.

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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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(opens in new window) H2020-MSCA-IF-2020

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Coordinator

FORSCHUNGSINSTITUT FUR MOLEKULARE PATHOLOGIE GESELLSCHAFT MBH
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.

€ 186 167,04
Address
CAMPUS-VIENNA-BIOCENTER 1
1030 Wien
Austria

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Region
Ostösterreich Wien Wien
Activity type
Private for-profit entities (excluding 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.

€ 186 167,04
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