Informations générales
Intitulé de l'offre : PhD Student (M/F): Characterization of a protein involved in the regulation of retinal neurogenesis by the retinal pigment epithelium (H/F)
Référence : UMR8003-DAMCAR-001
Nombre de Postes : 1
Lieu de travail : PARIS 06
Date de publication : mardi 14 octobre 2025
Type de contrat : CDD Doctorant
Durée du contrat : 36 mois
Date de début de la thèse : 17 novembre 2025
Quotité de travail : Complet
Rémunération : 2200 € gross monthly
Section(s) CN : 25 - Neurobiologie moléculaire et cellulaire, neurophysiologie
Description du sujet de thèse
The construction of the nervous system requires that the proper number and types of neurons are generated by neural progenitor cells in specific locations, at precise developmental times. Defects in these processes will result in abnormal formation of neuronal circuits with functional consequences that constitute the cause of neurodevelopmental diseases such as albinism. Indeed, all forms of albinism show visual deficits that result from alterations in the developing neural retina, originating from defects in the retinal pigment epithelium (RPE), a layer of epithelial cells that surround the neural retina. Here, we will take advantage of this feature to study how neurogenesis is regulated by extrinsic factors coming from surrounding cells. Most genes in albinism are related to melanosomes and melanin synthesis, but a recently identified gene has been involved in albinism-like retinal and optic nerve defects but without defect of the melanin pathway (FHONDA syndrome). This interesting candidate may thus unveil downstream processes linking melanogenesis to neurogenesis regulation. The protein involved in FHONDA syndrome is SNAT8, an amino acid transporter whose function is not well characterized. The thesis project is part of a collaboration between SPPIN and the Vision Institute and will aim to characterize the subcellular localization and transport and/or sensor function of the SNAT8 protein. Using in vivo (mouse) and in vitro (RPE cells and retinal organoids) models, combined with loss of function by CRISPR/Cas9 to mimic mutations found in both diseases, we will characterize the role of SNAT8 in the RPE and the ciliary margin zone as well as its effect on neurogenesis and its link with albinism. The deciphering of the cellular and molecular mechanisms underlying these two rare diseases will shed new light on the processes of visual system development.
Contexte de travail
SPPIN is a neuroscience research institute of the CNRS and Université Paris Cité located on the Saints-Germain-des-Prés campus whose objective is to characterize the mechanisms underlying brain functions, from synaptic transmission to the activity of neuronal networks and how this translates into specific behaviors in healthy and pathological conditions. To achieve these objectives, SPPIN adopts a multidisciplinary approach combining optical microscopy, electrophysiology, biochemistry, molecular biology, and behavior analysis and conducts studies at different scales.
Contraintes et risques
None