In vivo and in vitro axonal transport investigations in diverse models of MND/ALS

Project summary

Axonal transport maintains neuronal homeostasis by ensuring the long-range delivery of several cargoes, including cytoskeletal components, organelles, signalling molecules and RNA between proximal and distal neuronal compartments. As a result, perturbations in axonal transport have severe consequences for neuronal homeostasis and function. Indeed, axonal transport is perturbed in many neurodegenerative disorders, including motor neuron disease (MND)/amyotrophic lateral sclerosis(ALS).

In this project, we will assess axonal transport dynamics of distinct intracellular organelles (e.g., signalling endosomes, mitochondria, lysosomes, neurotrophic factors) in both mouse and human models of MND/ALS. The in vivo component will assess axonal transport in several mouse models of MND/ALS that are currently available at UQ. This will be complemented by the in vitro component that will assess transport dynamics in motor neurons derived from human induced pluripotent stem cells harbouring diverse MND/ALS patient mutations.

 

An in vivo axonal transport example video taken from the sciatic nerve of a live, anaesthetised mouse (for a detailed protocol see the following link-  https://www.jove.com/v/63471/expanding-the-toolkit-for-in-vivo-imaging-of-axonal-transport). Signalling endosomes (magenta), which are important structures carrying signalling molecules and survival factors, are being trafficked in the retrograde direction (i.e., right to left) from axon termini embedded in skeletal muscle and are travelling to the motor neuron cell body located in the spinal cord.