Description du sujet de thèse

Structural mapping of gene regulation using ultrafast photochemistry: a multidisciplinary approach to DNA conformational dynamics. Summary: This interdisciplinary project is developing an innovative method for studying the three-dimensional structure of DNA and its role in gene regulation. By combining ultrafast laser irradiation (5 nanoseconds) and nanopore sequencing, we 'freeze' the local conformation of DNA by inducing molecular modifications sensitive to its geometry. These structural alterations are then detected via subtle variations in the electrical current generated as the DNA passes through nanopores, enabling high-resolution mapping. Our preliminary results on bacterial plasmids reveal a sensitivity to changes in DNA torsion and coiling, essential for gene activity. The approach integrates artificial intelligence models and molecular simulations to link structure, dynamics, and function. Applicable to entire genomes, this methodology opens up prospects in fundamental research (allosteric regulation mechanisms) and personalized medicine (study of epigenetic alterations in cancerology). The project relies on a multidisciplinary consortium of physicists, biologists, and data science experts to establish a new paradigm for understanding gene expression at the molecular level.
Collaboration: The study will be conducted in collaboration with a researcher from the CQSB CNRS/Sorbonne University laboratory.

Contexte de travail

Structures, Properties and Modelling of Solids. CentraleSupélec/CNRS UMR8580
Ecole Doctorale Interface, Université Paris-Saclay
Thematic : Physics of macromolecular complexes of biological interest