PhD grant: Molecular modeling of DNA damage in the cell nucleus

The DNASTRIX project aims at investigating and quantifying how nuclear mechanics can be altered by forces issued from the cellular environment, and what are some key genomic implications of such mechanical processes, potentially involved in many human diseases from the cellular down to the molecular scale.

To reach such challenging objectives we are pushing the limits of an ensemble of innovative techniques based on micro-electromechanical systems (MEMS) devices, under active development in our laboratories, by which we can apply controlled forces to both molecular aggregates [1], and to whole living cells, while performing real-time fluorescence and confocal imaging [2].

In parallel, we leverage a theoretical and computer modeling program of all-atom and coarse-grained molecular dynamics (MD) of the key proteins participating in the mechanical actions transmitted to the nucleus and chromatin from the cellular environment, and whole-cell micro-mechanical modeling, to elucidate the multi-scale details of mechanical stress transfer to the nuclear constituents [3].

Therefore, the aims of this project are twofold and parallel:

$ In a first part of work, we will focus on observing and quantifying the mechanical link between extranuclear cell structures and nucleus;

$ In the second part we will track chromatin reorganization, and identify possible damage to chromatin and DNA from mechanical forces.

The main subect of this PhD grant is centered on the theory and modelling part of the work (See below, requisites for the candidates).

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] Pekin, D., et al., IEEE 33rd Int. Conf. on 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)

IEMN is the CNRS Institute of Nanotechnology and Microelectronics of the University of Lille. With near to 500 staff and students, and with a 1500sqm clean room for hi-tech fabrications, it is the largest French nanotechnology institute north of Paris.

The IEMN Physics group, led by prof. F. Cleri, develops both fundamental and applied research activities in quantum physics, nanotechnology and nanomaterials, surface force and probe microscopy, meta-materials, nanoacoustics, biophysics.

The successful PhD candidate must have a good background in at least three of the following areas: applied mathematics, computational modelling, fundamental physics, biophysics, statistical mechanics, molecular modelling, basic cell biology, bioinformatics.

Working knowledge of Linux/Unix, C/C++/Fortran, Python is a title of preference.

NOTE: the position is already open and will be started as soon as filled by the best candidate. The dates indicated below are purely indicative.