PhD M/F Bioimaging of bacterial media labelled with luminescent bioorthogonal chemical reporters: influence of the nano-environment in the development of biofilms

Job Description

Thesis Subject

Many bacteria have developed the ability to produce polysaccharide capsules that mimic the host's glycans, thereby protecting them from the immune system and acting as matrices in the formation of biofilms responsible for the majority of bacterial infections, particularly in hospital environments. Bacteria are also capable of developing flexible protein fibers called pili, which play a role in adhesion, motility and biofilm formation. The aim of this PhD project is to characterize the physicochemical conditions that enable the development of bacterial biofilms.
There is indeed a need for chemical biology tools to detect nano-environments conducive to the formation of these biofilms. Combined with glycan metabolic engineering, bioorthogonal chemistry is used to label certain glycans constituting bacterial cell walls (e.g. lipopolysaccharides, peptidoglycans, glycolipids) with luminescent probes. The luminescent markers selected will be fluorescent molecules whose photophysical properties (spectra and lifetimes) are sensitive to the nano-environment of bacterial capsules, in particular the viscosity of the medium, polarity and pH. The bacteria labelled in this way can then be imaged using confocal fluorescence microscopy, and the local physicochemical properties will be elucidated through lifetime fluorescence imaging. Furthermore, the development of biofilms will be characterized using super-resolution microscopy (STED, PALM-STORM) and FLIM-FRET (Förster Resonance Energy Transfer). These results will enable the physicochemical parameters of the bacterial environment to be correlated with biofilm formation.
The candidate will be involved in all stages of the project: the organic synthesis of clickable luminescent probes and their metabolisation by bacterial cell walls in samples (E. coli, Acinetobacter) will be carried out at the UGSF laboratory (University of Lille). The photophysical properties of these probes will be characterized in solution using steady-state and time-resolved spectroscopy at LASIRE, prior to imaging the labelled bacterial samples using FLIM, FLIM-FRET and super-resolution techniques. Microscopy data will be processed using advanced data analysis methods developed by the DyNaChem team at LASIRE.
We are looking for a highly motivated candidate with a Master's degree in Chemistry, who is interested in understanding the photophysical properties of fluorescent probes in biological systems using various spectroscopic and microscopic methods. Experience in applying these methods and processing the collected data would be a real asset. An interest in organic synthesis and the preparation of biological samples is essential. As part of this project, the successful candidate will be required to interact, exchange ideas and work alongside chemists, physical chemists and biologists, and must therefore be open to interdisciplinary research. Good communication skills in English (written and spoken) are required.

Your Work Environment

This research project is proposed as part of the ANR BIG_TReX project (ANR-24-CE44-5061): Bioorthogonal Iridium probes for Glycan Time-Resolved photoluminescence and X-ray nanoimaging. It is led by Prof. Cédric Lion (UGSF laboratory, University of Lille) and is the result of a collaboration between chemists, physical chemists and biologists from the UGSF, LASIRE and the STROBE laboratory (INSERM, University of Grenoble Alpes).
The characterisation of the probes and fluorescence imaging will be carried out at LASIRE (UMR 8516, University of Lille, Building C8). The successful candidate will have access to the microscopes developed by the DyNaChem team, as well as to LASIRE's platform for stationary and time-resolved spectroscopy. The synthesis of clickable luminescent probes and their metabolism by bacteria will be carried out at UGSF (UMR 8576, University of Lille, Building C9) under the supervision of Cédric Lion.
LASIRE is a sector falling under the protection of scientific and technical potential (PPST) and therefore, in accordance with regulations, requires that the candidate's hiring be authorized by the competent authority at the MESR.

Constraints and risks

NA

Compensation and benefits

Compensation

2300 € gross monthly

Annual leave and RTT

44 jours

Remote Working practice and compensation

Pratique et indemnisation du TT

Transport

Prise en charge à 75% du coût et forfait mobilité durable jusqu’à 300€

About the offer

About the CNRS

The CNRS is a major player in fundamental research on a global scale. The CNRS is the only French organization active in all scientific fields. Its unique position as a multi-specialist allows it to bring together different disciplines to address the most important challenges of the contemporary world, in connection with the actors of change.

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