Reference : UMR5237-DOMHEL-003
Workplace : MONTPELLIER
Date of publication : Monday, July 25, 2022
Scientific Responsible name : Dom Helmlinger & Peggy Raynaud
Type of Contract : PhD Student contract / Thesis offer
Contract Period : 36 months
Start date of the thesis : 3 October 2022
Proportion of work : Full time
Remuneration : 2 135,00 € gross monthly
Description of the thesis topic
Transcription involves the coordinated activities of a multitude of regulatory factors. An important class of regulators has chromatin modifying or –remodeling activities and function as co-activators during transcription initiation. Co-activators are typically multifunctional complexes that integrate regulatory information from promoter elements, transcription factors, and chromatin marks. Despite the advent of functional genomics, understanding how these factors establish specific gene expression programs remains challenging, likely because our view of their function is static. Here we propose a systems biology approach combining kinetic analyses, innovative transcriptomic approaches, and computational modelling to address this issue. The PhD student will measure the effects of co-activators on the temporal dynamics of transcription, nucleosome modifications, and general transcription factor assembly, allowing the ordering of mechanistic events. In collaboration with a team of physicists in Strasbourg, we will integrate these data into a stochastic biophysical model of transcription regulation by co-activators, which predictions will be tested experimentally. Overall, we expect this PhD project to make an important contribution in the transcription field, by identifying the principles governing the gene-specific effects of co-activators and better understanding how these properties sustain both robustness and plasticity of gene expression in response to perturbations.
Constraints and risks
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