CHEMBIOHISTONE | Expanding the chemical biology toolkit for the studies of histone post-translational modifications (PTMs)

Summary
Studying biomolecules in living cells is an important step towards understanding the cause and development of diseases. However, the existing tools dedicated to the study of biomolecules often lack generality and pose disturbance to the biological systems. Although bioorthogonal chemistry plays an important role in biomolecule studies, there are only a handful of bioorthogonal reactions that can modify these molecules in vivo.
In this project, we will develop a novel biocompatible reaction that can be widely used for modifying biomolecules both in vitro and in vivo. We will then employ the reaction to reveal the biological significance of post-translational modifications (PTMs) of histones proteins by using two strategies. First, the histone mimics that are not accessible by the existing methods will be synthesized. These histone mimics can serve as important models for us to understand the interactions between histones and their regulating enzymes. Second, real-time imaging of histone PTMs in living cells will be made possible by using a chemical biology approach. This approach can minimize the disturbance to the three-dimensional structure of the nucleosome, thereby providing a true image of dynamic histone PTMs during cellular processes.
In short, this multidisciplinary project lies on the interface of organic chemistry, biochemistry, and cell biology, with an aim to enable the in-depth studies of the unknown aspect of epigenetics.
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More information & hyperlinks
Web resources: https://cordis.europa.eu/project/id/708685
Start date: 01-11-2016
End date: 31-10-2018
Total budget - Public funding: 183 454,80 Euro - 183 454,00 Euro
Cordis data

Original description

Studying biomolecules in living cells is an important step towards understanding the cause and development of diseases. However, the existing tools dedicated to the study of biomolecules often lack generality and pose disturbance to the biological systems. Although bioorthogonal chemistry plays an important role in biomolecule studies, there are only a handful of bioorthogonal reactions that can modify these molecules in vivo.
In this project, we will develop a novel biocompatible reaction that can be widely used for modifying biomolecules both in vitro and in vivo. We will then employ the reaction to reveal the biological significance of post-translational modifications (PTMs) of histones proteins by using two strategies. First, the histone mimics that are not accessible by the existing methods will be synthesized. These histone mimics can serve as important models for us to understand the interactions between histones and their regulating enzymes. Second, real-time imaging of histone PTMs in living cells will be made possible by using a chemical biology approach. This approach can minimize the disturbance to the three-dimensional structure of the nucleosome, thereby providing a true image of dynamic histone PTMs during cellular processes.
In short, this multidisciplinary project lies on the interface of organic chemistry, biochemistry, and cell biology, with an aim to enable the in-depth studies of the unknown aspect of epigenetics.

Status

TERMINATED

Call topic

MSCA-IF-2015-EF

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-2015
MSCA-IF-2015-EF Marie Skłodowska-Curie Individual Fellowships (IF-EF)