Job ID: 118124

PhD project: Axonal zoning: interplay between presynapses and the periodic actin-spectrin scaffold

Position: Ph.D. Student

Deadline: 14 April 2024

Employment Start Date: 1 October 2024

Contract Length: 3 years

City: Marseille

Country: France

Institution: Aix-Marseille Université

Department: INP

Description:

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. This project is one of the 13 proposed projects. Not all proposed projects will be funded, check our website for details.

Axonal zoning: interplay between presynapses and the periodic actin-spectrin scaffold 

 

State of the art
Axons grow and maintain extended and complex arborizations thanks to a specialized organization of the axonal cytoskeleton, with numerous branches contacting downstream cells via presynaptic boutons. Within the last decade, our knowledge of this unique architecture has been transformed by the discovery of a submembrane periodic scaffold made of actin and spectrin lining the axon shaft1, and by the delineation of distinct actin nanostructures within presynapses, where this scaffold is absent2. Yet the patterning of presynaptic boutons along the shaft, and how the periodic scaffold is rearranged to allow for the formation or disappearance of a bouton, remains unknown. 

Objectives
We want to understand how the axon is patterned between scaffold-lined shaft segments and scaffold-free presynapses, and if the actin-spectrin scaffold itself has a role in regulating the presence of presynaptic boutons. We hypothesize that this is linked to an insulating role of the submembrane scaffold which restricts endocytosis (as we showed recently4) and exocytosis along the axon. We will this elucidate the dynamic relationship between the scaffold, endo/exocytosis, and presynapse formation during neuronal development in cultured hippocampal neurons. 

Methods
We have built a recognized expertise of using super-resolution microscopy to dissect the nano-architecture of the axonal cytoskeleton3. We are now developing new approaches to visualize the 190 nm-periodic scaffold in living neurons, adding a dynamic dimension to our understanding of its organization and roles. We have also developed ways to visualize endocytosis and exocytosis along the axon, distinguishing shaft segments and presynapses, as well as correlative methods to link endo/exocytosis sites to the nanoscale architecture of the cytoskeleton. These advanced methods will be used to visualize the transformation of the actin-spectrin scaffold during presynapse formation and the emergence of the synaptic vesicle exo/endocytic cycle, in control and perturbed conditions where the scaffold is disassembled or over-stabilized. 

Expected results
We expect to obtain crucial insights on the cell-autonomous mechanism of axonal compartmentation and synaptic plasticity, revealing a new physiological role for the periodic actin-spectrin scaffold in this process. 

Feasibility
The team is currently composed of 11 people including strong technical support (2 technicians, 1 engineer). Key methods for this project are currently developed thanks to works of post-doctoral fellows funded by ANR and FRM, which will be able to help the PhD student start their project. 

Expected candidate profile
We are looking for a motivated candidate with experience on some of the following: advanced microscopy, live-cell imaging, quantitative biology, working with cultured neurons. Don’t hesitate to contact marie-jeanne.papandreou@univ-amu.fr if you have any question or want to know more. 

  1. Papandréou & Leterrier. Mol Cell Neurosci, 2018 Sep;91:151-159. 10.1016/j.mcn.2018.05.003
  2. Bingham et al. J Cell Biol, 2023; 222(10):e202208110. 10.1083/jcb.202208110
  3. Leterrier et al. Nature RevNeurosci, 2017; 18(12):713-726. 10.1038/nrn.2017.129
  4. Wernert et al. bioRxiv, 2023 Dec 19. 10.1101/2023.12.19.572337