Description du sujet de thèse

Alzheimer's disease (AD) is characterized by the spread of toxic proteins (Tau and Aβ) via exosomes, contributing to disease progression. Similarly, extracellular vesicles containing mitochondria (EVMs) may facilitate the transfer of dysfunctional mitochondria between brain cells, thereby accelerating neurodegeneration. However, the role of EVMs in AD remains poorly understood.
Our recent findings (manuscript under revision) have, for the first time, revealed that dysfunctional mitochondria in AD model cells, induced by the accumulation of C-terminal fragments of APP (APP-CTFs), trigger the secretion of EVMs carrying dysfunctional mitochondria. Moreover, AD-derived EVMs actively contribute to the transfer of mitochondrial pathology between cells in vitro.
Based on these observations, this project aims to explore how EVMs mediate the transfer of dysfunctional mitochondria from a neuronal perspective and how they influence neuronal function, plasticity, and cognition in AD.
The development of this project builds on our expertise in mitochondrial structure and function, as well as on validated protocols we have recently established protocols for the study of extracellular vesicles. Our team has long-standing experience in studying AD using both cellular and mouse models. This project will enhance our understanding of intercellular communication in AD by identifying EVMs as key mediators of mitochondrial dysfunction and synaptic alterations, potentially uncovering new therapeutic targets.

Contexte de travail

The position is based at the Institute of Molecular and Cellular Pharmacology (IPMC) in Valbonne – Sophia Antipolis (Alpes-Maritimes). The IPMC is a joint research unit (UMR 7275) established between the CNRS, Inserm, and Université Côte d'Azur (250 staff members, 8,000 m² of facilities). Its 20 research teams benefit from a high-level technological environment in integrative biology, electrophysiology, molecular and cellular biology, imaging, flow cytometry, biomolecule analysis, and functional genomics. In particular, the shared technical platforms for animal experimentation and the team's own equipment enable detailed phenotyping of mice.
The PhD student will join the ALZPARK team, led by Mounia Chami and Cristine Alves Da Costa. The team's research aims to understand the pathophysiological mechanisms of Alzheimer's disease (AD) and Parkinson's disease (PD).

Le poste se situe dans un secteur relevant de la protection du potentiel scientifique et technique (PPST), et nécessite donc, conformément à la réglementation, que votre arrivée soit autorisée par l'autorité compétente du MESR.

Contraintes et risques

Work involving GMOs and animal models

Informations complémentaires

Knowledge of the fundamental basics of neurodegenerative diseases
Training in neurobiology
Molecular and cellular biology
Basic experience in animal experimentation
Ability to analyze data
Histology, immunohistochemistry
Strong organizational skills, rigor and method, motivation, and team spirit
Proficiency in written and spoken English