Targeting Synaptic 'eat Me' Signals to Prevent Excessive Synaptic Engulfment By Microglia and Reduce Synaptic Loss in Alzheimer’s Disease

**Targeting synaptic 'Eat Me' signals to prevent excessive synaptic engulfment by microglia and reduce synaptic loss in Alzheimer’s Disease**:

- Réf **ABG-129185**
- Sujet de Thèse
- 06/03/2025
- Contrat doctoral
- NeuroSchool, Aix-Marseille Université
- Lieu de travail- Marseille - Provence-Alpes-Côte d'Azur - France
- Intitulé du sujet- Targeting synaptic 'Eat Me' signals to prevent excessive synaptic engulfment by microglia and reduce synaptic loss in Alzheimer’s Disease
- Champs scientifiques- Psychologie, neurosciences
- Biologie
- Santé, médecine humaine, vétérinaire
- Mots clés- neuroscience, neurobiology, cognition, neural networks, brain, behavior, neurodegenerative diseases, ageing,

**Description du sujet**:
**_The NeuroSchool PhD Program of Aix-Marseille University (France) has launched its annual calls for PhD contracts for students with a master's degree in a non-French university and for international co-supervised PhDs._**

**_This project is one of the proposed projects. Not all proposed projects will be funded, check our website for details._**

**Objectives**: The global objective is to reduce synaptic loss in Alzheimer’s disease and slow cognitive decline. The first objective involves testing a chimeric molecule developed by the team to convert the aberrant “eat me” signal from synapses to microglia into a “don’t eat me” signal, preventing excessive synaptic engulfment. In the second objective, the student will design and test additional molecules targeting alternative pathways involved in aberrant synaptic in AD.

**Methods**: 1/ The team has developed a chimeric molecule that converts the aberrant “eat me” signal from synapses to microglia into a “don’t eat me” signal, preventing excessive synaptic engulfment. Based on promising preliminary in vitro results, the student will assess the impact of this molecule on synaptic and neuronal loss in an AD mouse model (P301S), as well as its effects on cognitive function (behavior analysis), synaptic activity (electrophysiology), structure (super-resolution microscopy), and protein changes (proteomics).

**Feasibility**: All the necessary equipment is available at INP or through a network of collaborators. The team has strong expertise in synaptic loss, and microglial reactivity in Alzheimer’s disease. Mouse models are actively breeding, behavioral tests are optimized, and co-culture models are established in the lab. Promising preliminary in vitro data further support the project’s relevance and potential for success. The first 1.5 years focused on data collection and processing for the first objective, and the following 1.5 years for the second objective.

**Prise de fonction**:

- 01/10/2025

**Nature du financement**:

- Contrat doctoral

**Précisions sur le financement**:

- 3 years

**Présentation établissement et labo d'accueil**:

- NeuroSchool, Aix-Marseille Université

Within **Aix Marseille Université, NeuroMarseille**brings together 8 research laboratories and NeuroSchool, a graduate school in neuroscience, to increase the attractiveness of the university, international collaborations, interdisciplinarity, links with the clinical and industrial worlds and the integration of students into professional life.

Launched in July 2018, **NeuroSchool**unifies and harmonizes the training of the third year of the Bachelor of Life Sciences (Neuroscience track), the Master's and the PhD in Neuroscience.

**Site web**:
**Intitulé du doctorat**:

- Doctorat de neurosciences

**Pays d'obtention du doctorat**:

- France

**Etablissement délivrant le doctorat**:

- Aix Marseille Université

**Ecole doctorale**:

- Sciences de la vie et de la santé
- Master's degree from a non-French university in neuroscience or related field
- Fluent in English- 14/04/2025