Description du sujet de thèse

This thesis aims at using fluorescence microscopy/nanoscopy and lifetime imaging (FLIM) to characterize tumor-on-chips and other 3D cancer co-culture systems, including organoids, with the final intent to investigate the microenvironment impact on cancer cell response to therapies.
The project is part of the DEEPSEE project (International Chair: High performance 3D bioimaging, ISITE ULNE) which centers on the development within DyNaChem team (http://lasir.cnrs.fr/dynachem/) of new fluorescence microscope modalities for very fast 3D imaging combined with low phototoxicity.
The PhD candidate will monitor the response of 3D cancer cell cultures to therapies using state-of-the-art 3D fluorescence microscopy, aiming to visualize multiple parameters simultaneously in order to capture the processes occurring inside these tumor models. He/she will be expected to handle the sample preparation and culturing, perform the labeling and fluorescence imaging, and to analyze the resulting datasets in order to uncover correlations between oxygen levels, pH and cell death, as well as more generally fluorescence signals generated by genetically encoded biosensors and nanoparticles.

Thesis program: it will consist (1st year) in getting trained with fluorescence-based microscopy methods and assessing the function of cancer cells with a 3D videomicroscope built in the lab by a post-doctoral fellow. The candidate will then aim at optimizing the use of probes/sensors for multiplex analysis (spectra and lifetime) of cell response in real time, with minimal exposure times to limit phototoxicity and photobleaching. With the help of a post-doctoral fellow on thorough imaging analysis, the third year of the thesis will be devoted to link measured biophysical parameters and the response to various targeted therapies, and to write the thesis.

Candidate Profile: Candidates should have a Master's degree in biology or physics, with a background in fluorescence microscopy, image analysis, and cell biology. He/she should be highly motivated to work in an international and interdisciplinary project, in which a great team spirit is required.

Contexte de travail

This thesis will be will be co-hosted by LASIRE (Team Dynamic, Nanoscopy and chemometrics, http://lasir.cnrs.fr/dynachem/) and CANTHER labs (Cancer heterogeneity, plasticity and resistance to therapies, https://www.canther.fr/), and will be directed by Dr. Alessandro Furlan (CANTHER Lab, Oncolille Institute, Univ. Lille, https://www.canther.fr/), and co-supervised by Dr. Olivier Devos (LASIRE lab, Univ. Lille) and Prof. Peter Dedecker (KULeuven).

Le poste se situe dans un secteur relevant de la protection du potentiel scientifique et technique (PPST), et nécessite donc, conformément à la réglementation, que votre arrivée soit autorisée par l'autorité compétente du MESR.