PhD thesis in cellular neurobiology (M/F)

Job Description

Thesis Subject

The assembly of functional neuronal circuits requires the coordinated execution of several developmental processes, including neuronal migration, axon growth and guidance, and synaptogenesis. These processes critically depend on dynamic and finely regulated remodelling of the actin cytoskeleton and microtubules. During axon growth, the growth cone integrates extracellular guidance cues and converts them into cytoskeletal remodelling events, thereby generating the mechanical forces required for its motility. This motility also relies on the dynamics of adhesion structures to the extracellular matrix. Genetic evidence increasingly indicates that mutations disrupting these mechanisms can impair the development of neuronal circuits and contribute to the onset of neurodevelopmental disorders (NDD), such as autism spectrum disorders and intellectual disability.

Our research aims to understand the molecular mechanisms that govern cytoskeletal dynamics during nervous system development and how their disruption by mutations may contribute to NDDs. In recent years, we have identified key roles for the microtubule-associated protein Navigator-1 (NAV1) in axon growth and guidance. Notably, we have shown that NAV1 controls these processes by coordinating the dynamics of microtubules and actin network within the axonal growth cone. More recently, our work has revealed that NAV1 also regulates cell adhesion dynamics during the directed migration of non-neuronal cells by functionally coupling cytoskeletal and adhesion dynamics. These findings suggest that NAV1 may play a similar role in regulating adhesion in neurons to control growth cone motility during axonal guidance. Furthermore, we have identified mutations in the NAV1 gene in individuals with NDDs, suggesting that disruption of its functions may contribute to defects in neuronal circuit formation during development.

The proposed PhD project aims to further characterize the molecular mechanisms by which NAV1 regulates axon growth and guidance, and to determine the functional impact of NDD-associated mutations. Three specific objectives will be pursued: (i) to characterize the role of NAV1 in regulating adhesion dynamics during axonal navigation; (ii) to elucidate the molecular mechanisms by which NAV1 integrates extracellular guidance signals with cytoskeletal remodelling and adhesion dynamics in neurons; and (iii) to determine the effects of NDD-associated NAV1 mutations on its molecular and cellular functions. This project will combine complementary approaches in cellular neurobiology, molecular biochemistry, and developmental biology, using primary cultures of mouse neurons and cell lines, as well as high-resolution live-cell imaging techniques.

Your Work Environment

The PhD student will join the “Signalling and Cytoskeleton Dynamics” research team at the Cell Biology Research Centre of Montpellier (CRBM). A thesis monitoring committee will be established to oversee the progress of the research through annual meetings. The student will regularly present their results during the team's biweekly meetings and once a year to the entire laboratory. They will also receive specific technical training required to carry out their research project. The research program in which the PhD project is embedded is conducted in collaboration with several French and international laboratories.

Constraints and risks

No specific safety requirements.

Compensation and benefits

Compensation

2300 € gross monthly

Annual leave and RTT

44 jours

Remote Working practice and compensation

Pratique et indemnisation du TT

Transport

Prise en charge à 75% du coût et forfait mobilité durable jusqu’à 300€

About the offer

About the CNRS

The CNRS is a major player in fundamental research on a global scale. The CNRS is the only French organization active in all scientific fields. Its unique position as a multi-specialist allows it to bring together different disciplines to address the most important challenges of the contemporary world, in connection with the actors of change.

CNRS

The research professions