The PhD student will be enrolled in the CARe program.

Deadline for application:  April 15th 2023

Starting date: September/October 2023

Working context:

Infinity (Toulouse Institute for Infectious and Inflammatory Disease) is joint research unit of the French National Institute of Health and Medical Research (Inserm), the National Center for Scientific Research (CNRS), and the University of Toulouse. Infinity is a dynamic research institute comprised of 14 teams about 300 people and is located in Toulouse, a lively and fast-growing city in the Southwest of France with the 2nd largest student population. Within Infinity, the PhD candidate will work in the research team “Antigen Presenting Cells in T cell responses” led by Nicolas Fazilleau. This project is in close collaboration with ImmunXperts, a Q² Solutions company, localized at Gosselies (Belgium). During the PhD program, an internship of several months will be performed in this biotech company.

Working project:

The PhD candidate will study the development and biological roles of the human Tfr pool during physiological and ageing humoral responses.

Germinal centers (GCs) are the lifeblood of protective humoral immunity, require complex regulation that can decline with time, increasing vulnerability to infectious diseases and limiting vaccination benefits of elderly population. The integrity of GCs relied upon T follicular regulatory cells (Tfr), a regulatory subset that ensure antibody affinity for pathogens while decreasing self-recognition. Despite displaying a dual function in GCs reaction, Tfr cells were originally described as affiliated exclusively to Tregs (“natural” Tfr cells, nTfr), a population expressing autoreactive T-cell receptors (TCRs). More recently, we challenged this dogma by the description, in human tonsils, of a Tfr subset, descending from Tfh cells (“induced” Tfr cells, iTfr). However, the biologic role of a heterogenic Tfr pool in human and its impact on ageing immune responses are currently unknown.

The long-term goal of the proposed PhD program is to determine the biological role of the Tfr pool heterogeneity during GC response in humans and how ageing impacts this balance contributing thus to immune dysfunction. Our working hypothesis is that two distinct pathways shape the human Tfr pool, and immunopathology could result when one developmental pathway takes the lead. Our final ambition is to develop strategies to influence the Tfr pool composition that will improve the vaccine response of the elderly population.

Technical approaches:

– Single cell RNA sequencing on human T follicular populations

– Multiplex microscopy of human tissues

– Development of human lymphoid organoïds and in vitro functional assays

– Recruitment and immunophenotype by multiparametric flow cytometry of an “ageing” cohort

Expected profile:

We are looking for a highly motivated and dynamic PhD candidate with strong interest in immunology and excellent communication skills. Previous experienced with data analysis in R would be appreciated.

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