Three-year PhD position in Neurosciences: pathogenic mechanisms in Alzheimer's disease

Alzheimer’s disease (AD) represents one of the most significant scientific and socio-economic challenges of the 21st century. Hallmarks of AD include aggregates of amyloid-β (Aβ) and tau proteins, as well as neuroinflammation and gliosis, which collectively lead to synaptic and neuronal loss, forming the basis of cognitive decline. While the mechanisms underlying neurodegeneration in AD remain incompletely understood, recent evidence highlights the pivotal role of microglial reactivity, influenced significantly by TREM2 and associated inflammatory responses. Both Aβ and tau pathologies exacerbate microglial reactivity, aggravating disease progression and neurodegeneration. However, the specific roles of microglia in Aβ- or tau-induced neurotoxicity remain unclear.

This study aims to investigate the proteomic changes in microglia caused by Aβ and tau pathologies, a critical step toward identifying potential therapeutic targets for halting or slowing AD progression.

The selected candidate will engage in a cutting-edge research project that seeks to elucidate the molecular mechanisms underlying microglia-driven neurodegeneration in AD. Specifically, the project will involve identifying proteomic differences and similarities in microglial reactivity induced by Aβ and tau pathologies, leveraging microglia-specific metabolic labeling of the proteome in Aβ and tau mouse models. The research will encompass the use of genetically modified mice and a range of techniques, including proteomics, biochemical assays, molecular and cell biology methods, as well as histopathological analysis.

The INP is a center of training and research that combines basic and translational research to study the organization, function and interaction of neural cells, as well as the molecular and cellular basis of major brain diseases. The INP is part of the Centre of Excellence in Neurodegeneration (CoEN) and offers an internationally competitive research environment with state-of-the-art facilities. The PhD student will be supervised by Dr. Maud Gratuze. The project will be developed at the Faculty of Medicine, located in the centre of Marseille, a few kilometers from the magnificent seafront, the Calanques National Park and the charm of inland Provence, all ideally suited to outdoor and cultural activities.

To apply, candidates must hold an internationally-recognized Master-equivalent degree in biology, neurosciences or related fields. No restrictions of citizenship apply to the position. Previous knowledge/experience on either Alzheimer’s pathogenesis, proteomics, basic methods on biochemistry and molecular biology, cell culture, confocal/super-resolution microscopy, behavioral experiments will be highly appreciated but is not mandatory.

Preferable: comfortable with mouse handling

• SOFT SKILLS Autonomy, work ethic, critical thinking, adaptability, teamwork, motivation, curiosity, problem-solving