Description du sujet de thèse

Lanthanide complexes with push-pull antennas for luminescence sensitisation have demonstrated their strong potential for cellular imaging, thanks in particular to their two-photon absorption properties, which enable excitation in the near infrared. As part of the MAGELLAN project, we are seeking to develop luminescent probes for multiplex biological imaging of cells, with two objectives: (1) to develop Yb3+-based probes for NIR-NIR imaging and (2) to develop probes capable of performing spatio-temporal imaging of O2 consumption and the production of reactive oxygen species (ROS = HOCl, H2O2) in macrophages, using Tb3+, Eu3+, Sm3+ and/or Yb3+ probes. To this end, we will design conjugates between lanthanide complexes and peptides or biological macromolecules (polysaccharides, polylysine, zymosan) in which the peptide or macromolecule will enable the lanthanide complex to be localised in the cytosol or phagosome of the macrophage or will constrain it in the extracellular environment. The PhD student recruited will have three objectives: (1) the synthesis and characterisation of lanthanide-based probes, (2) the evaluation in solution of their ability to detect ROS, and (2) their evaluation for two-photon microscopy and monitoring of ROS production or O2 consumption with macrophages.

Activities: The PhD student recruited will be responsible for synthesising macrocycles with push-pull antennas for lanthanide complexation, synthesising conjugates, purifying them by HPLC, conducting luminescence spectroscopic studies to characterise them in solution, and conducting cell microscopy studies.

Profile: The successful candidate will have a strong background in organic and bio(in)organic chemistry with solid experience in organic and/or peptide synthesis. They must have a keen interest in the chemistry/biology interface, particularly coordination chemistry, spectroscopy and fluorescence microscopy imaging. The candidate must be proficient in chromatography techniques for the purification of organic molecules and peptides, as well as in the characterisation of molecules by NMR. Knowledge of fluorescence would be an advantage.

Contexte de travail

The postdoc recruited will join the 'Metallopeptides' group at the Chemistry and Biology Laboratory (joint research unit of CEA-Grenoble, Univ. Grenoble Alpes and CNRS). This thesis is part of the MAGELLAN project, funded by the French National Research Agency (ANR), in collaboration with a team of spectroscopists specialising in lanthanides at ENS Lyon (Olivier Maury's group) a team of biologists specialising in macrophages at the IAB in Grenoble (Olivier Destaing's group), working closely with the IAB's MicroCell microscopy platform (Alexei Grichine).