Thesis financed by the Mission for Transversal and Interdisciplinary Initiatives of the CNRS (80prime program).
The project combines experimental molecular genetics and theoretical physics of life. The aim is to explore how the association between nuclear bodies formed by phase separation and certain regions of the genome participates in the expression of the genes they contain.
The regulation of gene expression at the right place and at the right time is generally explained by the recognition of DNA sequences by dedicated proteins, under the control of so-called epigenetic regulations. The aim of our project is to better understand an aspect of this regulation, which is still little studied: the role played by the physical properties of the human genome and its immediate environment, constituted by the nucleoplasm and the organelles, or 'nuclear bodies', which are located there. The focus will be on the role of ions and electrostatic interactions in the phase separation mechanisms controlling the formation of 'nuclear bodies'.
The study will rely on various experimental approaches (chromosome conformation capture, high salt insolubilization, fluorescence imaging, etc.) on living cells, normal or genetically modified, by varying the local physical conditions. It will help to understand the mechanisms involved in the predisposition to certain cancers.
Work Context :
The Institute of Molecular Genetics of Montpellier is a joint research unit of CNRS and the University of Montpellier, with 180 people divided into 17 research groups, 9 common services (5 of which are shared with other units in health biology of the CNRS campus) and 9 technological and scientific platforms, at the cutting edge of technology (http://biocampus.cnrs.fr), in an international atmosphere.
The IGMM is a multidisciplinary institute whose work has an international impact in molecular and cellular biology.
Lesne et al. Genes 10 :1049 (2019)
Baudement et al. Genome Research, 28:1733 (2018)
Carrivain et al. Soft Matter 8 :9285 (2012)
Jablonski et al. Human Genomics 16:2 (2022)