Description du sujet de thèse

Targeting of specific sets of RNA molecules to various subcellular localization has recently emerged as a prominent mechanism enabling tight spatiotemporal control of protein production. RNA localization is particularly important in neuronal cells, which extend long axonal and dendritic branches that must locally respond to different cues. While it is now well established that the axonal and dendritic compartments of neuronal cells contain specific reservoirs of mRNAs transported from the soma and available for onsite translation, how the axonal and dendritic RNA landscapes are locally organized and regulated to integrate external local signals is to date unclear.
The objective of the PhD project will be to dissect the mechanisms underlying the compartment-specific recruitment of mRNAs along axons. First, the student will dissect the contribution of activity cues. Through artificial inactivation/activation of specific populations of neurons, (s)he will test whether similar (or distinct) populations of mRNAs get recruited to distinct compartments in response to specific activation. In parallel, (s)he will explore if learning and memory paradigms trigger the recruitment of RNAs to specific synaptic compartments. Second, the student will study the cellular machineries involved in local RNA recruitment and tethering. Combining functional approaches, (live) imaging and quantitative smFISH, (s)he will particularly focus on the contribution of localized RNA binding proteins and of the actin cytoskeleton in this process.
Together, this project will unravel the mechanistic bases underlying sub-cellular compartmentalization of mRNAs in neuronal cells in vivo. We will not only dissect the molecular machineries implicated in this process, but also identify the cues they respond to in an in vivo context.

Contexte de travail

The Valrose Institute of Biology (iBV) is an international research institute comprising 27 teams and approximately 250 members. It has three supervisory bodies: CNRS, Inserm, and Université Côte d'Azur. The Institute is located in Nice, on the Valrose science campus.
The team is composed of approximately ten members (http://ibv.unice.fr/research-team/besse/).

Contraintes et risques

adaptation of schedules to experimental protocols