PhD student (M/F) in immunology at the interface with chemistry – Development of an innovative nano/biotherapy for rheumatoid arthritis

About this position

The PhD thesis (Doctoral School "Life and Health" - ED414) will be conducted within the Immunology, Immunopathology and Therapeutic Chemistry Laboratory (CNRS UPR3572), located at the Institute of Molecular and Cellular Biology in Strasbourg (IBMC, France), which brings together approximately 250 researchers, engineers, technicians, (post)doctoral fellows, and interns. The Institute is located on the central campus (Esplanade) near the city center and is easily accessible by public transport. A university restaurant as well as an administrative restaurant (subsidized rate) and health services are available on campus or nearby.

The Unit possesses unique, internationally recognized expertise in autoimmune diseases and nanomedicine, particularly in the development of carbon nanomaterials, such as carbon nanotubes, for biomedical applications and the evaluation of their potential toxicity. This PhD thesis topic is part of a project funded by the French National Research Agency (ANR) that brings together partners from Strasbourg and Paris. It will be carried out under the direction of Dr. Hélène Dumortier (immunologist) in close collaboration with the laboratory's team of chemists, particularly Dr. Cécilia Ménard-Moyon, and a postdoctoral researcher.

The laboratory has previously obtained solid preliminary results, supporting the project's feasibility. All the necessary equipment is available at the IBMC or on neighboring platforms.

Rheumatoid arthritis (RA) is the most common autoimmune disease, affecting approximately 0.5% of the population in France. This disease progresses in flare-ups due to inflammation of the synovial membrane of the joints, leading to joint destruction and pain. Despite undeniable progress in recent years, RA remains incurable, and it is therefore essential to continue our efforts to develop new treatments.

Macrophages play a key role in the pathogenesis of RA by contributing to the development of inflammation and joint destruction. This research program aims to develop an innovative therapy combining the targeted delivery of methotrexate (MTX) via a vector (carbon nanotubes, CNTs) with the selective elimination of inflammatory cells (including activated macrophages) in arthritic joints, thus resulting in a drastic reduction of inflammation and other symptoms of RA. This treatment relies on photothermal therapy triggered by near-infrared (NIR) light.

It generates localized heat within the inflammatory cells of arthritic joints via the phagocytosis of a photothermal agent (in this case, CNTs), leading to the specific death of these cells. The CNTs are coated with the cell membrane of macrophages to specifically target and promote their accumulation in the inflamed synovium, where they are internalized by phagocytic inflammatory cells. Local NIR irradiation induces the selective thermal elimination of these cells.

Furthermore, the use of CNTs as a carrier for methotrexate (MTX) allows for high concentrations of this standard anti-rheumatic drug to be delivered to the inflamed joints, thus reducing the administered dose and consequently its side effects.

In this context, the PhD student will be responsible for i) evaluating the biological efficacy (effect of MTX, targeting and elimination of macrophages) of CNT-based conjugates in vitro, ii) studying the biodistribution and targeting efficacy of these conjugates in vivo in a murine model of collagen-induced arthritis and finally iii) evaluating their therapeutic efficacy in this same model in order to provide a preclinical proof of concept.

Prerequisites:

• Education : Master's or engineering level

• Strong interest in interdisciplinarity

• Solid background in cell biology and immunology

• Knowledge of techniques using immunolabeling, particularly flow cytometry