Stage M2S3 (2019-2020)

Human infertility is the inability to conceive after two years of regular unprotected intercourses and is due to a male factor in approximately 50% of cases. Our goal is to identify human genes involved in human gametogenesis. A second potential consequence is the identification of genes involved in the ontogeny of human PGCs.
One of the main difficulties encountered in such projects is the recruitment of informative patients. In order to solve this, we have established collaborations in Turkey, North Africa (Algeria, Tunisia, Morocco) and the Middle East (Jordan, Iran, Lebanon, Saudi Arabia), where patients often come from small communities with little or no immigration and with a high degree of consanguinity. Husband and wife are thus often related and susceptible to harbor the same rare dormant recessive mutation they have inherited from a common ancestor. They are particularly suited for this type of genetically heterogeneous pathologies, as it allows the development of intra-familial strategies based on the identification of genomic regions with common parental haplotypes (homozygosity mapping).
A whole genome sequencing strategy to identify genes which, when mutated are responsible for an infertility phenotype, can be applied to these patients. This approach has been used successfully for couple of genes, SPATA16 and DPY19L2, TEX15 have been identified upon studying family cases (Dam, Koscinski et al. 2007; Koscinski, Elinati et al. 2011, Okutman et al 2015).
These results will contribute to a better understanding of the physiopathological process of human reproduction and spermatogenesis. In the lab, we are focusing now on meiosis defects by studying azoospermic patients with maturation arrest, and infertile women producing oocytes blocked at germinal vesicule stage. The candidate will contribute to characterize the implicated genes using multidisciplinary approaches such as linkage analysis, next generation sequencing. According to the type of mutation found different strategies can be applied to prove the deleterious effect of the mutation on the encoded protein. Functional analysis of the identified protein will be conducted. The type of analysis will depend on the putative function of the protein.
Compétences souhaitées : Des compétences à la fois théoriques et pratiques en Biologie du Développement, en Biologie Cellulaire et Moléculaire et Bioinformatique sont souhaitées.
Motivation, rigueur et esprit d'équipe sont indispensables.
Bon niveau d’anglais indispensable.
Expertises qui seront acquises au cours de la formation :
Expertise scientifique : Génétique humaine, analyse bibliographique, identifications des questions scientifiques, développement des stratégies scientifiques, mise en place des expériences, analyse critique des résultats, Formulation d’hypothèses de travail, rédaction d’articles
Expertise expérimentale : Biologie Moléculaire et cellulaire, analyse génomique , Bioinformatique, Culture Cellulaire, FACS