Job ID: 12560

Ph.D. Student in VALBONNE/France

Position: Ph.D. Student

Deadline: 10 June 2021

Employment Start Date: 1 October 2021

Contract Length: 36 months

City: Valbonne

Country: France

Institution: Institut de Pharmacologie Moléculaire et Cellulaire (IPMC)

Department: CNRS UMR 7275 - Université Côte d'Azur


We are looking for a talented PhD student to investigate the impact of a Fragile X missense mutation in glutamate receptor trafficking. We recently demonstrated that FMRP is sumoylated in vivo and that its activity-dependent sumoylation is critical to the neuronal function. Sumoylation is the covalent conjugation of the Small Ubiquitin-like MOdifier (SUMO) protein to lysine residues of target proteins. It modulates the dynamics of multi-protein complexes. Several FXS missense mutations lead to amino-acid changes that are close to the active SUMO sites of FMRP. This raises the exciting possibility that these mutations directly affect the regulation of FMRP sumoylation, impacting its function, and consequently leading to FXS. We focused on the recurrent FXS R138Q mutation, which is close to the main active SUMO site of FMRP. We generated a Knock-in mouse model expressing the FXS R138Q mutation in FMRP (R138Q-KI). We published that the density of dendritic spines is increased with critical alterations in the surface levels of glutamatergic AMPA receptors (AMPAR) leading to significant synaptic plasticity defects and to impaired cognitive and social behaviours. The selected student will use biochemical and cell-imaging techniques to unravel the molecular basis of these receptor trafficking defects.

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previous job ID: 28811