Development of photoswitchable MAO-B inhibitors targeting inflammation in osteoarthritis

The ANR project PhotoROS is a multidisciplinary project aimed at developing innovative tools to study and control the activity of monoamine oxidase B (MAO-B), an enzyme involved in oxidative stress and the inflammatory diseases, particularly osteoarthritis. MAO-B generates reactive oxygen species (ROS) in the mitochondria of chondrocytes and synoviocytes, triggering activation of the NLRP3 inflammasome and cartilage degradation. The project aims to develop photoswitchable MAO-B inhibitors whose activity can be reversibly modulated by light (photopharmacology), enabling precise spatiotemporal control of enzymatic activity.

The project is structured around six tasks : 1) in silico studies (molecular docking); 2) synthesis of photoswitchable inhibitors ; 3) determination of photophysical and photochemical properties ; 4) in vitro assessment of MAO-B inhibitory activity; 5) cytotoxicity assays and cell culture ; 6) modulation of MAO-B activity in human cells and evaluation of anti-inflammatory properties

This PhD project will be carried out in collaboration between two research laboratories:

CiTCoM UMR CNRS 8038, Inserm U1268, UFR de Pharmacie (Pr. Ludovic Jean, Dr. Lucas Pagès) – Expertise in medicinal chemistry, docking, organic synthesis, and photoswitch compounds

INSERM UMR-S 1124 T3S, UFR Sciences Fondamentales et Biomédicales, Université Paris Cité (Pr. Didier Borderie) – Expertise in biochemistry, oxidative stress, and osteoarthritis biology

CiTCoM UMR 8038, 4 avenue de l’Observatoire, F-75006 Paris

T3S INSERM UMR-S 1124, 45 rue des Saints Pères F-75006 Paris

We are looking for a candidate with a chemistry-biology background and the following skills :

Organic synthesis, purification and characterisation techniques (NMR, MS, HPLC, etc.).

in vitro assays, cell culture (flow cytometry).

Ability to take initiative, propose innovative ideas, and work independently.

Communication skills to present research findings effectively.