Description of the thesis topic

The DNASTRIX project aims to study and quantify how nuclear mechanics can be modified by forces originating from the cellular environment, and what are the key genomic implications of these mechanical processes, potentially involved in many human diseases, from the cellular to the molecular scale. To achieve such ambitious goals, we are pushing the boundaries of a set of innovative techniques based on micro-electromechanical systems (MEMS) devices, under active development in our laboratories, thanks to which we can apply controlled forces both to molecular aggregates [1], and to whole living cells, while performing real-time fluorescence and confocal imaging [2]. In parallel, we are exploiting a program for all-atom, coarse-grained theoretical and computational molecular dynamics (MD) modeling of key proteins participating in mechanical actions transmitted to the nucleus and chromatin from the cellular environment, as well as whole micro-cells. mechanical modeling, to elucidate the multi-scale details of the transfer of mechanical stresses to nuclear constituents [3].
The objectives of this project are therefore twofold and parallel:
$ In the first part of the project, we will focus on observing and quantifying the mechanical link between extranuclear cellular structures and the nucleus;
$ In the second part, we will monitor chromatin reorganization and identify possible chromatin and DNA damage due to mechanical forces.
The main focus of this doctoral fellowship is the theory and modeling portion of the project (see below, prerequisites for applicants).
You can find more background information in the following references:
[1] Perret, G., et al., Microsys. Nanoeng. (Nature) 2, 16062, DOI : 10.1038/micronano.2016.62 (2016)

[2] Pékin, D., et al., IEEE 33rd Int. Conf. sur MEMS, 62-65, DOI : 10.1109/MEMS46641.2020.9056362 (2020)
[3] Cleri, F., Giordano, S., Blossey, R., J. Mol. Biol. 435, 168263, DOI : 10.1016/j.jmb.2023.168263 (2023)

Work Context

The CNRS IEMN institute in Lille (Hauts-de-France) brings together in a single structure the bulk of regional research in a vast scientific field ranging from the physics of materials and nanostructures to telecommunications systems and acoustic and microwave instrumentation. The IEMN Physics group studies thin films, hetero and periodic structures, individual or assembled biomolecules and 0D/1D/2D materials of great interest for technological breakthroughs in electronics, optics, acoustics, optoelectronics and nanotechnology. The NAMASTE team of the Physics group develops theoretical and experimental subjects of soft matter, biophysics and micro-physics of cancer.

The position is located in a sector under the protection of scientific and technical potential (PPST), and therefore requires, in accordance with the regulations, that your arrival is authorized by the competent authority of the MESR.

Constraints and risks

No risk associated with experimental manipulations. The candidate will be able to attend experiments conducted in the DNASTRIX project's partner laboratories, but their work remains primarily theoretical (development and application of biophysical mathematical models). Short-term travel in France and abroad is expected.

Additional Information

Doctoral contract grant funded by the ANR project "DNASTRIX: DNA damage at nuclear constrictions".