Recent research suggests a balanced synergy between the host immune system and microbiome.

Gut microbiome dysbiosis could alter this synergy and aggravate disease severity in Primary Antibody Deficiencies (PAD). A large portion of PAD are at high risk of developing infectious and non-infectious complications, including allergies, gastrointestinal inflammation, malignancies, and autoimmunity, causing significant morbidity and mortality. The biomarkers of this deleterious evolution are not well understood.

The goal of this PhD project is to develop a dynamic prediction model based on multi-marker profiles for immune microbiome dysregulation and associated disease progression in PAD. To achieve this goal, the main objective of this program is are 1) to accurately predict antibody-bound taxa from intestinal samples, 2) to assess the virome change in high-risk PAD; 3) to develop a dynamic prediction model for high-risk PAD based on multi-marker profiles.

The PhD project will be based on our previous research studies (metagenomic data from cohorts of subjects/patients for whom clinical and immunological data have been collected longitudinally) and lab established biobank with stool and serum directly derived from patients, and on which viromic approaches will be carried out. Using simulated and experimental data, we demonstrate novel probability-based scores that adjust for the compositional nature of relative abundance data to accurately quantify taxon-level IgA binding. To generate machine learning predictors with risk score estimation for disease progression in PAD we will employ in our prediction algorithms we will incorporate additional biological factors as input into ML models, such as bacteriome, mycobiome and virome composition, microbial functional and immune profiles, host-immune interactions data.

Overall, our PhD project constitutes a multidisciplinary and intersectoral training programme with a balanced combination of hands-on research training, international research stays, teaching courses and network-wide events on scientific and transferable skills, enabling future academic, hospital and industry collaborations.

PhD student: Tea SONICKI

PhD supervisors: Dr Lejla IMAMOVIC (Co-director), Pr Guy GOROCHOV (Director)

Research laboratory: Département d’Immunologie Hôpitaux Universitaires Pitié Salpêtrière - Charles Foix - SU-CNRS-INSERM