Détails de l'offre
- Type de poste: PhD/Doctorat
- Secteur : Public
- Localité : France
- Limite de candidature : 02/11/2021
- Profil de poste:
Recherche et innovation
- Domaine(s) :
Microbiologie et Immunologie
Job offer available on this link.
Paris – Ile-de-France – France
PhD Proposal abstract
Invasive pneumococcal diseases (IPD) is one of major risk of death for children with primary immunodeficiencies (ID) associated with antibody or complement deficiency. However, the majority of IPD occurs in children without known deficiency and despite anti-pneumococcal vaccination. We hypothesize that these “idiopathic” IPD may be caused by single-gene inborn errors of immunity. We intend to investigate patients with proven idiopathic IPD. We will identify and characterize the underlying genetic defects by a strategy combining powerful genome-wide explorations and in-depth functional experiments.
Streptococcus pneumoniae is a Gram-positive encapsulated bacterium, which is almost ubiquitous, with the prevalence of asymptomatic carriage in the rhinopharynx approaching 90% in healthy children. However, in rare cases, pneumococcus may cause invasive diseases, such as arthritis, septicemia, and meningitis (designated as IPD). IPD is life-threatening, not only because of its rapid clinical course, but also because of the spread of antibiotic-resistant bacterial strains. Most children with IPD are between the ages of 3 months and 3 years. Non-conjugated pneumococcal vaccines are poorly protective in children under 18 months of age, and the conjugated vaccines protect against even fewer serotypes. Thus, childhood IPD poses a major public health problem.
Environmental factors, such as socioeconomic conditions, probably account for the higher incidence of IPD in developing countries. However, the occurrence and rarity of IPD in Western countries suggest that host factors also play a prominent role in its pathogenesis. Some acquired (HIV, splecnectomy, cancers, …) and inherited host factors including drepanocytosis and certain IEIs (1) have been identified. Among the inherited host factors, children with ICA or impaired complement- or Ab- mediated opsonization are specifically susceptible to encapsulated bacteria, pneumococcus in particular. Remarkably, the greatest risk factor for IPD is IPD itself, with a 2-4% recurrence rate.
2. Doffinger et al. Nat Genet, 2001. 27(3): p. 277-85
3. Boisson. Human Genetics, 2020. 139(1) p. 981–991 4.
4. Boisson et al.. Nat Immunol, 2012. 13(12): p. 1178-86. 5.
5. Boisson et al. J Exp Med, 2015. 212(6): p. 939-51.
6. Boisson et al. J Clin Invest, 2018.
7. Li, J, … …, Boisson, B. J Exp Med, 2021. 218(11). 8.
8. Picard et al.Science, 2003. 299(5615): p. 2076-9.
9. von Bernuth, et al.. Science, 2008. 321(5889): p. 691-6.
10. Gaschignard et al. C. Clin Infect Dis, 2014. 59(2) p. 244-251
Nature du financement : Financement public/privé
About the Imagine Intitute
First European centers of research, care and education on genetic diseases, the Imagine Institute aims to understand them and cure them. The Institute brings together 1000 of the best doctors, researchers and healthcare personnel in a creative architecture of synergies. Today Imagine is focused on its ambition to change the lives of families affected by genetic diseases.
Intitulé du doctorat : Doctorat de Biologie
Pays d’obtention du doctorat : France
Ecole doctorale : Profil du candidat
The program is intended for students who hold a Master’s degree (or equivalent) from a university outside France and who have not worked or resided in France for more than 12 months in the 3 years preceding their recruitment.
The selection of the PPU-IMAGINE program is organized by Institut Imagine and selected students carry out their research in one of Institut Imagine lab.
Expected profile / where to apply
Genetic and molecular biology training course
Exome/Genome or RNAseq and computational skills
Six-month lab experience