NeuroCyto: the neuronal cytoskeleton in health and disease

Team leader: 
Description: 

 

The team started in 2017 as part of the CNRS ATIP program. At NeuroCyto, we are neuronal cell biologists: we want to understand how neurons are organized at the cellular level.

How do neurons differentiate, then build and maintain their complex arborization? How do they establish and conserve their polarity, with the axon and dendrites allowing to send and receive signals? Numerous processes contribute to this organization: elaboration of the cell architecture (thanks to the cytoskeleton), protein transport inside the cell (with diffusion and motor proteins), segregation into distinct compartments (such as axon, synapses, dendritic spines…).

We apply advanced microscopy techniques to directly observe molecular assemblies at the nanoscale in neurons, revealing how they organize the neuron and shape its physiology.

 

Public Summary: 

“NeuroCyto: the neuronal cytoskeleton in physiology and disease” is a team that was created in 2017, as part of  the Neuropathophysiology Institute (INP, CNRS-Aix Marseille University UMR 7051) in beautiful Marseille, France. The team currently has six members, and we welcome trainees all year long. Motivated students are always welcome to contact us! We aim at building a thriving team to make the best possible science by nurturing openness, exchange, and the excitement of discoveries big and small. At NeuroCyto, we want to understand how neurons are organized at the cellular level. How do they differentiate, then build and maintain their complex arborization? How do they establish and conserve their polarity, with the axon and dendrites allowing to send and receive signals? Numerous processes contribute to this organization: elaboration of the cell architecture (thanks to the cytoskeleton), protein transport inside the cell (with diffusion and motor proteins), segregation into distinct compartments (such as an axon, synapses, dendritic spines…). The NeuroCyto team applies advanced microscopy techniques to directly observe molecular assemblies at the nanoscale level in neurons, revealing how they organize the neuron and shape its physiology.

Research topics: 

We are currently focusing on actin organization within axons. Several new axonal actin structures have been discovered by us and others, including submembrane actin rings and intra-axonal actin hotspots and trails. We want to understand the functions of these structures and their relevance for physiological processes such as axonal transport and proper functioning of presynaptic boutons. To do so, we take advantage of the beautiful model of hippocampal neurons in low-density culture, so we can visualize the intricate morphology of individual neurons and follow individual axons. We combine live-cell imaging, targeted manipulations and super-resolution microscopy to connect the dynamic behavior of axonal components to the nanoscale organization of the cytoskeleton, and we devote substantial efforts to implement innovative strategies for the labeling, observation and analysis of these processes. We explore the pathophysiological relevance of our finding by studying cellular models of Alzheimer’s disease, as axonal transport and presynaptic function are compromised in the early stages of the disease.

Role of actin-based nanostructures in axons

Following the identification of new axonal actin structures (rings, hotspots and trails), we want to understand their molecular architecture, assembly mechanism and potential interplay. This is done thanks to a combination of live-cell imaging and super-resolution microscopy techniques as well as innovative strategies to selectively perturb actin within axons. 

New approaches for labeling, imaging and analysis in super-resolution microscopy

To reveal the organization of the axon, an intricate cellular compartment with extensive length and branching, we use optical super-resolution microscopy. We are specialists of Single Molecule Localization Microscopy (SMLM), and we keep working to push the methods, implementing and testing new techniques as soon as they appear. This includes labeling methods for highly-multiplexed acquisition such as DNA-PAINT, automated acquisition strategies, and new image analysis algorithms.

Cell biology of Alzheimer’s disease in relevant cellular models

Impairment of axonal transport and presynaptic release are early-stage events in Alzheimer’s disease. Using our cell biology background, we want to gain a better understanding of why this happens by studying the nanoscale organization of the axon in Alzheimer’s disease models. Starting with classical rodent models, we want to turn to human models thanks to neurons obtained from induced pluripotent stem cells developed by the Nivet team. These models are still poorly characterized at the subcellular organization level, and it will be interesting to look for specific defects in neurons derived from Alzheimer’s disease patients

Partners: 

                  

News

  1. Just out: NeuroCyto team in Science
  2. New article from the NeuroCyto Team in Neuron
  3. 2 INP researchers in La Marseillaise "Provence Terre de Science" 

    Each week-end the local newspaper La Marseillaise puts the spotligh on a scientific topic and on a team of research in a scientific page called "Provence Terre de Science". After the page about Alzheimer disease last year (see here), INP research has been highligthed with the interview of Jean Marc Sabatier (Cytoskeleton and Neurophysiopathology team) for his work on venoms, and then Christophe Letterier (NeuroCyto team) for his work on superresolution imaging of neurons, in La Marseillaise week-end editions of may 22nd-24th and

  4. Two articles from the NeuroCyto team in Nature Communications

    The NeuroCyto team has two new articles just out in Nature Communications! Click for more details >>

  5. FRM Équipe 2021 to the NeuroCyto team

    The NeuroCyto team was awarded an “Équipe” grant from the Fondation pour la Recherche Médicale. With more than 400,000 euros over three years, it will allow the team to investigate the organization and role of actin at presynapses using advanced micromanipulation and cutting edge super-resolution microscopy.

  6. Christophe Leterrier (NeuroCyto team) in Nature Materials

    Christophe Leterrier from the NeuroCyto team just published a study in collaboration with the Cytomorpho lab  - Manuel Théry & Laurent Blanchoin, CEA Paris/Grenoble. Entitled “Self-repair protects microtubules from destruction by molecular motors”, this work demonstrates how motor proteins kinesins and dynein can damage microtubule while walking on them, triggering repair by incorporation of new tubulin monomers inside the microtubule lattice. It was published on Jan.

  7. Christophe Leterrier (NeuroCyto team) in the Journal of Neuroscience: “A Pictorial History of the Neuronal Cytoskeleton”

    Christophe Leterrier, leader of the NeuroCyto team, just published a special review for the 40th anniversary issue of the Journal of Neuroscience. Entitled “A Pictorial History of the Neuronal Cytoskeleton”, it is a journey through the history of the neuronal cytoskeleton in pictures.

  8. The NeuroCyto team receives two ANR grants in 2020

    The NeuroCyto team led by Christophe Leterrier was awarded two collaborative ANR grants in the 2020 call. The first project, “How actin/spectrin scaffold shapes axonal physiology” (ASHA), is coordinated by C. Leterrier in collaboration with the teams of Stéphane Vassilopoulos (Institut de Myologie, Paris) and Emmanuel Nivet at INP.

Pages

Gallery

Open Positions

ANR-funded post-doctoral position in the NeuroCyto lab (C. Leterrier) at INP

The NeuroCyto lab is looking to hire a postdoctoral fellow for an exciting project bridging the nanoscale architecture of axons and their cellular functioning!

About the position and project

This postdoctoral position is funded for two years, with the idea of looking for fellowships after these first years. The position is available from January 1st, 2022. It is supported by an Agence Nationale de la Recherche (ANR 2021-2024) grant focusing on the functions and dysfunctions of the periodic actin/spectrin scaffold found along axons. The project will use cell biology approaches on neuronal cultures and advanced microscopy techniques (live-cell imaging, super-resolution microscopy) with quantitative workflows. Established collaborations will allow investigating the axonal ultrastructure by electron microscopy and extending results to human neurons from induced pluripotent stem cells. The postdoc will drive the project with supervision and mentoring from group leader Christophe Leterrier: devising, performing, and analyzing experiments, working with other members of the team, preparing publications from the project.

About the team and environment - more at https://www.neurocytolab.org

The NeuroCyto lab is part of the NeuroPhysiopathology Institute (INP, https://inp.univ-amu.fr/en) located on the Timone campus of Aix-Marseille University, in the center of Marseille, France. We are a young and thriving team of around 10 people (researchers, PhD students, engineers, techs) led by Christophe Leterrier. The overarching aim of the team is to understand the architecture of the neuronal cytoskeleton to explain how it builds, maintains, and transforms neuronal organization and function. We have a recognized expertise in applying cutting-edge microscopy techniques, in particular Single Molecule Localization Microscopy (SMLM) to neuronal cell biology. In addition, we have strong ties with the newly revamped cellular imaging facility at INP which offers a range of super-resolutive approaches. In the team, we aim at making ambitious and rigorous science by fostering a positive environment based on respect, team spirit, good communication and mentoring.

About the profile

We are looking for candidates with a PhD in cell biology, neuroscience, or microscopy with strong motivation to push things forward. Skills in neuronal cell biology, cell culture (including neurons), sample preparation, optical microscopy (possibly super-resolution), image analysis (e.g., ImageJ/Fiji, python) are a plus. Discipline for promptly and rigorously designing, conducting, and analyzing experiments as well as motivation to develop new workflows are expected. Taste for interdisciplinary work, team spirit, ability to interact and collaborate with junior researchers and general sense of camaraderie and motivation to learn are a must.

About the application

Interested in this opportunity? Please apply before January 1st, 2022 by sending a CV, name of three references, and motivation letter stating why we should work together on this project to christophe.leterrier@univ-amu.fr. Don't hesitate to contact Christophe more informally if you have any question about the position.

Team publications