Investigating autophagy pathway dynamics at the neuromuscular junction
Autophagy is the primary waste recycling pathway in all our cells that targets and degrades misfolded proteins, aggregates and damaged organelles. Autophagy is essential for cell survival, bioenergetics, immunity and inflammation. Waste recycling by autophagy plays a pivotal role in highly metabolic tissue such as skeletal muscle and at the neuromuscular junction (NMJ – the chemical synapse connecting motor neurons and skeletal muscle fibres).
Changes in the structure and function of NMJs are hallmarks of neurodegenerative diseases such as motor neuron disease (MND). However, the status of autophagy at the NMJ in response to ageing and MND is poorly understood.
Before we can modulate autophagy pathway for therapeutic purposes, we need an understanding of cell-specific autophagy. Although many studies have investigated autophagy in tissue such as liver and kidney, autophagy dynamics at the NMJ and skeletal muscle remains under-explored.
This project will analyse muscle tissue from a novel transgenic autophagy reporter mouse model (RFP-EGFP-LC3) to quantify the effects of MND and ageing on muscle autophagy dynamics. Gastrocnemius and tibialis anterior muscle from MND mice as well as adult (6 months), middle-aged (12 months) and advanced aged (18 months) mice have been already collected.
The findings will reflect fundamental differences in autophagy pathway dynamics at the NMJ in responses to ageing and MND, and will inform therapeutic strategies development.
Our work will involve cryostat sectioning of muscle tissue, conducting immunohistochemistry, confocal microscopy and image analysis with computer software to quantify autophagy flux at the NMJ.
Take part in this project
Students who are applying to study at The Florey can register their interest in this project. Refer to our step-by-step guide to help you with your application.