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

Description

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.

Nature de finanement

Other funding

Desired profile

While not mandatory, prior knowledge or experience in the following areas will be highly valued: Alzheimer’s disease pathogenesis, Proteomics, Biochemical and molecular biology techniques, Cell culture, Confocal or super-resolution microscopy, Behavioral experiments.

Company

The INP is a premier center for training and research, combining basic and translational studies to investigate neural cell organization, function, and interactions, as well as the molecular and cellular basis of major brain diseases. As part of the Centre of Excellence in Neurodegeneration (CoEN), the INP provides an internationally competitive research environment equipped with state-of-the-art facilities.

The successful PhD candidate will be supervised by Dr. Maud Gratuze and will conduct the project at the Faculty of Medicine, located in the heart of Marseille. This location offers proximity to the stunning seafront, the Calanques National Park, and the picturesque countryside of Provence, ideal for outdoor and cultural activities