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H/F PhD 3 years contrat to Decode the role of enhancer priming on transcriptional bursting

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Français - Anglais

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General information

Reference : UMR5535-MOULAG-004
Workplace : MONTPELLIER
Date of publication : Tuesday, May 19, 2020
Scientific Responsible name : Mounia Lagha, Ovidiu Radulescu
Type of Contract : PhD Student contract / Thesis offer
Contract Period : 36 months
Start date of the thesis : 1 October 2020
Proportion of work : Full time
Remuneration : 2 135,00 € gross monthly

Description of the thesis topic

In order to generate a functional organism, cell fate decisions must be taken at the right place and at the right time. Decades of genetic studies in Drosophila have dissected the gene regulatory networks responsible for the establishment of precise patterns of gene expression. In certain cases, network architecture reveals error correction mechanisms. However, recent live imaging studies show that transcription occurs in a random on/off manner called “bursts”. The details of how transcription factors control
bursting are unknown and are the focus of this proposal. Our project is concerned with a particular class of TFs called pioneer factors, such as Zelda. To study the impact of TF pioneer factors on transcriptional bursting in single cells, we will employ quantitative live imaging of transcription (MS2/MCP) combined to an innovative signal processing approach, able to position each single polymerase initiation event for each nucleus in vivo. With a view to understanding how order emerges from stochastic local events, both microscopic and coarse-grained mesoscopic models will be developed. The micro-meso relationship will be rigorously studied in the framework of limit theorems for Markov processes.

Work Context

This project belongs to an interdisciplinary project in collaboration with three labs: Mounia Lagha, Ovidiu Radulescu and John Reinitz. The PhD student will be based in Montpellier and co-supervised by ML and OR but will travel regularly to Univ. Chicago to work with the Reinitz lab, where a second PhD student will be working on a related project. The experiments will be primarily performed in the Lagha lab and the mathematical modelling in the Radulescu lab.

The PhD student will be affiliated to I2S (Information, Structure, Systems) doctoral school in Montpellier

Constraints and risks

The PhD student, whose major role will be the mathematical modeling, will also be familiarized with the experimental
techniques and will contribute to data production and analysis in a proportion compatible with his major activity.

Confocal imaging, Genetics, Molecular Biology; Data analysis (image analysis, statistics, programming in R/Matlab or Python); Mathematical modelling (continuous- and discrete-time Markov processes).
Derive mesoscopic, coarse-grained models of noise in biological systems
Improve existing analysis methods of biological data
Understand the impact of noise on the precision in development of an organism

Additional Information

Detailed version of the thesis:
https://ovidiu-radulescu.yj.fr/stages/PhD_CNRS_CHICAGO_long.pdf

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