PhD project on the Immunomodulatory function of osteoclasts in normal and inflammatory conditions

A PhD position is proposed in team 2 on the immune function and diversity of osteoclasts

Immunomodulatory function of osteoclasts in normal and inflammatory conditions

Summary

Osteoclasts are the cells responsible for bone resorption. As members of the monocyte family, they also have an innate immune cell function that was neglected for a long time. Our team is among the very few number of teams specialized in the immune function of osteoclasts. Thanks to the new tools we developped to specifically analyze and purify osteoclasts, we recently showed that osteoclasts are antigen presenting cells that activate CD4+ T cells. We also demonstrated that they are heterogeneous and induce opposite immune responses depending on their origin and environment. This opens very novel perspectives for the treatment of pathologies related to bone destruction.
We recently identified specific transcriptional signatures for the different osteoclast subsets that highlighted a number of factors involved in immune function. The aims of this PhD project are: 1. To participate to the ongoing identitication of the functional pathways involved in the immune function of osteoclasts. 2. To validate the main relevant pathways in osteoclasts through functional assays in vitro and in vivo in mice. 3. To confirm the expression of the identified markers in osteoclasts from patients and evaluate them as new diagnostic markers or therapeutic target.As members of the monocyte family, osteoclasts are not only bone-resorbing cells but also innate immune cells that present antigens and activate T cell responses, a function that has been neglected for a long time. Recently, our team demonstrated the existence of 2 osteoclast populations based on their opposite effects on T cell activation. One is anti-inflammatory and induces regulatory T cells, while the other is pro-inflammatory and induces TNF-producing T cells. These data revealed that osteoclasts are a heterogeneous population of cells having broader function than just bone resorption. Very recently, we confirmed this heterogeneity by single cell-RNAseq analysis on pure mature osteoclasts that identified a more important diversity with different subsets having specific transcriptional signature including factors involved in immune responses. This is a very novel aspect of osteoclast biology that remains poorly understood.
The aims of this project are: 1. From our murine scRNAseq analysis, to identity functional pathways that can participate to the immune function of the different osteoclast subsets. 2. To validate these pathways and the markers associated to them in vitro through functional assays in osteoclasts and in vivo in mouse in healthy and inflammatory contexts related to the bone destruction (osteoporosis or Crohn’s disease). 3. To confirm the expression of these markers in osteoclasts from patients (osteoporosis or Crohn’s disease) and evaluate them as new prognosis or diagnostic markers.

Key words

Osteoimmunology, chronic inflammation, physiology, osteoporosis, human disease, animal models

To apply

We are seeking for a highly motivated and talented PhD student with a good knowledge in immunology and cell biology. Knowlegde in bioinformatics is a plus. Excellent team communication and organization skills are essential. French or English practice is mandatory. The PhD student will benefit from the facilities and stimulting environment of the Faculty of Medicine and will be enrolled in the Graduate School for Life and Health Sciences of the Université Côte d'Azur.

To apply, please send your CV, master records and motivation letter by e-mail to