Description du sujet de thèse

Alzheimer's disease (AD) is an irreversible age-related neurodegenerative disorder. Despite intensive research, there is still no effective treatment to prevent or halt the progression of AD. Studies conducted by my team have shown that early impairments in general autophagy and mitophagy are key causal factors contributing to the development of AD (Acta Neuropathologica 2021, Cell Death & Disease 2024, Acta Neuropathologica Communications 2024, Alzheimer's Research & Therapy 2025). However, the molecular mechanisms underlying these defects remain unknown. Moreover, the relevance of autophagy and mitophagy defects occurring in neurons in AD is still unclear.
This PhD project will develop interdisciplinary fundamental research with clinical impact. We will investigate the mechanisms underlying autophagy and mitophagy defects in AD ex vivo and at the cellular level in the brain of a mouse model of AD. We will assess these dysregulations in relation to mitochondrial function ex vivo. We will also develop innovative approaches to modulate autophagy and mitophagy in vivo and at the cellular level, and study their impact on Alzheimer's pathology. The results obtained will contribute to advancing our understanding of AD pathogenesis and will help develop new therapeutic approaches to prevent or slow down the disease.

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