Neurons are highly polarized cells with distinct sub-domains, including the axon responsible for signal transmission to target cells. To meet the challenge of functional maintenance in the axon, which can extend far from the soma, neurons rely on local protein synthesis from mRNAs that are transported, stored and translated in the axonal compartment. This process requires a tight regulation of ribosome distribution (functional units of protein synthesis) in the axonal compartment, which is essential for axon development, neurotransmission and plasticity, and may be defective in axons of the adult mammalian central nervous system (CNS) that fail to regrow after injury.
However, the mechanisms governing ribosome supply to axons remain completely elusive, partly because detecting ribosomes in axons has been technically difficult until recent advances in imaging. In addition, very little is known about the link between regulation of ribosome axonal supply in axons and their intrinsic regrowth capacity.
Here, we propose an interdisciplinary project to investigate axonal ribosome supply in relation to axon regrowth capacity, using subcellular imaging of individual axons regrowing from ex vivo retina explants, a gold-standard model to study CNS axon regrowth. Based on high-resolution real-time imaging together with a novel ribosome-tracking tool developed by the host laboratory, this project addresses the following aims:
1) optimization of high-resolution imaging of ribosomes in regrowing axons;
2) development of an analysis pipeline for automated detection and trajectory tracking;
3) correlative measurements of ribosome movements in relation to other organelles in axons;
4) data-driven modelling of axon regrowth capacity based on ribosome axonal supply.
Results will significantly advance our understanding of how ribosome supply is dynamically regulated in the axonal compartment during regrowth. Based on our combined expertise in neurobiology, optical imaging and computer vision, this project will investigate mechanisms of ribosome transport in the axon and their link to axon regrowth capacity after injury. Altogether, this project will set the basis to explore ribosome movement and storage in the axon, to predict how external cues impact it, and to evaluate potential therapeutic interventions to improve axon regrowth and/or limit axon degeneration in multiple neurological contexts.
However, the mechanisms governing ribosome supply to axons remain completely elusive, partly because detecting ribosomes in axons has been technically difficult until recent advances in imaging. In addition, very little is known about the link between regulation of ribosome axonal supply in axons and their intrinsic regrowth capacity.
Here, we propose an interdisciplinary project to investigate axonal ribosome supply in relation to axon regrowth capacity, using subcellular imaging of individual axons regrowing from ex vivo retina explants, a gold-standard model to study CNS axon regrowth. Based on high-resolution real-time imaging together with a novel ribosome-tracking tool developed by the host laboratory, this project addresses the following aims:
1) optimization of high-resolution imaging of ribosomes in regrowing axons;
2) development of an analysis pipeline for automated detection and trajectory tracking;
3) correlative measurements of ribosome movements in relation to other organelles in axons;
4) data-driven modelling of axon regrowth capacity based on ribosome axonal supply.
Results will significantly advance our understanding of how ribosome supply is dynamically regulated in the axonal compartment during regrowth. Based on our combined expertise in neurobiology, optical imaging and computer vision, this project will investigate mechanisms of ribosome transport in the axon and their link to axon regrowth capacity after injury. Altogether, this project will set the basis to explore ribosome movement and storage in the axon, to predict how external cues impact it, and to evaluate potential therapeutic interventions to improve axon regrowth and/or limit axon degeneration in multiple neurological contexts.
Supervisor
Dr Julia Schaeffer, Institut de Biologie du Développement Marseille, Aix-Marseille University
Co-Supervisor
Dr Séverine Dubuisson, Laboratoire d'Informatique et Systèmes, Aix-Marseille University
Intersectoral partner
Aziz Moqrich, Tafalgie Therapeutics, Marseille, France
International partner
Nina Miolane, University California Santa Barbara, Geometric Intelligence Lab - Electrical and Computer Engineering, USA