Project description

The incidence of systemic lupus erythematosus (SLE) and systemic sclerosis is markedly increased in women. Both sex hormones and X chromosomes might contribute to this sex bias. The dosage of X-linked genes is equilibrated between men and women due to the inactivation of one X chromosome (XCI) in female cells. However, XCI is incomplete, leading to increased expression of some X-linked genes, such as TLR7 (Souyris et al., Sci. Immunol. 2018). The objectives of this PhD project will be to investigate whether higher levels of TLR7 expression, arising from the escape of X-chromosome inactivation (XCI) are linked to increased risk of developing autoimmunity in experimental models of SLE. This will be achieved by exploring the relevance of TLR7 XCl escape to the pathophysiology of SLE and by assessing the functions of key human immune cell subsets implicated in disease development, in relationship to the dose of TLR7 (one copy or two copies) at single-cell resolution using state-of-the art technologies (RNA FISH, singlecell RNA seq) and news genetic mouse models recently developed in the lab.

Candidate profil

We are looking for :

• creative and highly motivated Ph.D. students of all nationalities strongly committed to research
• applicants must have an excellent M.Sc. or equivalent degree with a strong background in immunology and/or physiopathology
• Experience in flow cytometry and in vivo models will be a plus.

Start date of the thesis:

1st September or October, 2021

Salary:

PhD student, 3 year contract

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