STAGE Development of therapeutic approaches to reactivate fetal globin for the treatment of sickle cell disease

Date de mise à jour de l’offre

Imagine, Institut des maladies génétiques :

Créé à l’initiative des chercheurs et médecins de l’Hôpital Necker Enfants malades, l’Institut hospitalo-universitaire (IHU) sur les maladies génétiques Imagine développe des programmes scientifiques fondés sur une continuité entre recherche fondamentale, recherche clinique et soins innovants sur les maladies génétiques et les prédispositions génétiques aux maladies fréquentes, de l’enfance à l’âge adulte. Imagine a pour ambition d’accélérer la recherche en l’organisant au plus près du malade afin d’apporter les solutions diagnostiques et thérapeutiques attendues par les patients et leurs familles.

Description de la mission

Sickle cell disease (SCD) is a severe chronic anemia caused by a single point mutation in the adult β-globin gene and affects hundred thousand newborns worldwide annually. The sickle hemoglobin has the propensity to polymerize under deoxygenated conditions, resulting in the production of sickle-shaped red blood cells (RBCs) that can cause occlusions of small blood vessels, leading to impaired oxygen delivery to tissues, respiratory complications and organ damage. So far, the only curative treatment is represented by bone marrow transplantation from a compatible donor, but it is available to less than 30% of the patients. Therapies that are in the experimental stages include gene therapy and pharmacological intervention. In the latter approach, efforts are underway to identify compounds that raise the expression of the fetal -globin genes. The rational for this treatment is based on the long-standing observation that patients with linked mutations that trigger elevated -globin expression, which are normally expressed only during fetal life, experience a more benign clinical course of the disease. Unfortunately, both gene therapy and pharmacological therapies have potential drawbacks, such as the genotoxic risk and the systemic toxicity, respectively.
The aim of the proposed project is to provide the knowledge for developing safe therapies to SCD based on genome editing approaches aimed to increase -globin expression. The mechanisms and the regulatory elements that control the switch from fetal to adult globin gene expression will be studied at molecular level. Studies focused on the molecular mechanisms underlying the β-to--globin switching as well as on the evaluation of the efficacy and safety of these therapeutic approaches will be proposed during the internship. The student will apply novel molecular techniques (e.g. genome-wide genomic analyses and CRISPR/Cas9 technology) by using innovative cellular models.

Profil recherché

M2

Niveau de qualification requis

Bac + 4/5 et +
  • Employeur
    Imagine, Institut des maladies génétiques
  • Secteur d’activité de la structure
    Enseignement - Formation - Recherche
  • Effectif de la structure
    De 51 à 250 salariés
  • Type de stage ou contrat
    Stage pour lycéens et étudiants en formation initiale
  • Date prévisionnelle de démarrage
  • Durée du stage ou contrat
    Plus de 4 mois et jusqu'à 6 mois
  • Le stage est-il rémunéré ?
    Oui
  • Niveau de qualification requis

    Bac + 4/5 et +
  • Lieu du stage
    24 Boulevard du Montparnasse
    75015 PARIS 15E ARRONDISSEMENT
  • Accès et transports
    Montparnasse Duroc Falguière