Local Mrna Expression and Translation in Axon Regrowth

**Local mRNA expression and translation in axon regrowth**:

- Réf **ABG-129195**
- 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- Local mRNA expression and translation in axon regrowth
- 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._**

**State-of-the-art**: The intrinsic inability of injured adult CNS neurons to regenerate their axon is a primary barrier to functional reconnection. Our recent work showed, at the soma level, that mTOR-induced axon regrowth requires translation of specific mRNA subsets, independently of their transcriptional state. In addition, it is known that translation is locally regulated in neuronal compartments such as the axon, a critical process in circuit development and function. However, little is known about local translation in axon regeneration after CNS injury.

**Objectives**:**To unlock CNS axon regrowth, the project focuses on regulation of gene expression _in the axon itself_. We hypothesize that CNS axon regrowth depends on local translation of regrowth-associated mRNAs, a process that may be defective after injury, contributing to regeneration failure. The specific objectives are to:
1) Characterize the local mRNA content in regrowing axons

2) Characterize mRNA selective translation in regrowing axons

**Methods**: To identify locally translated mRNAs, we will study regrowth of injured retinal ganglion cells (RGCs) and compare adult wild-type (WT) RGCs with a regrowth-promoted capacity in adult mTOR-activated RGCs and with a high regrowth capacity in developing (post-natal day 0, P0) WT RGCs. We will use adult retina explant cultures, which offer access to the axonal compartment, RGC specificity and transposability to in vivo testing. Regrowing axons will be isolated from somas using transwell filters, which allow for compartment-specific profiling and ribosome-associated mRNA analysis using RNA-sequencing.

**Feasibility**: This project leverages our expertise in adult retina explant cultures (optimized in our previous work), ribosome immunoprecipitation, next-generation sequencing (NGS) analysis and histology. Mouse lines necessary in this project (Pten-floxed, RiboTag) are already available in the lab. We have submitted the project for ethical authorization so the procedures will be approved by the start of the PhD. The project will be conducted at IBDM, which has all essential facilities to carry out experiments.

**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