mcMINFLUX | Tracking conformational dynamics of cohesin with MINFLUX

Summary
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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More information & hyperlinks
Web resources: https://cordis.europa.eu/project/id/101033534
Start date: 01-03-2022
End date: 29-02-2024
Total budget - Public funding: 186 167,04 Euro - 186 167,00 Euro
Cordis data

Original description

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.

Status

TERMINATED

Call topic

MSCA-IF-2020

Update Date

28-04-2024
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Horizon 2020
H2020-EU.1. EXCELLENT SCIENCE
H2020-EU.1.3. EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions (MSCA)
H2020-EU.1.3.2. Nurturing excellence by means of cross-border and cross-sector mobility
H2020-MSCA-IF-2020
MSCA-IF-2020 Individual Fellowships