Stem cell disease modelling to investigate mechanisms of selective vulnerability of motor neurons

About the project

Motor neurons are amongst the longest neurons in the body with its axon extending up to a metre to connect target muscle. Accumulating evidence suggests independent pathomechanisms affect distinct cellular compartments of motor neurons – soma and axon – leading to motor neuron loss and axon degeneration, respectively.

The overarching aim of our research is to decipher the molecular pathomechanisms leading to selective vulnerability of motor neurons as observed in motor neuron disease. In addition, we also focus on understanding and exploit mechanisms that control axonal homeostasis to promote axonal maintenance and preserve axons from degeneration. To achieve this we use cutting edge technologies like human stem cell modelling including 3D organoid models, CRISPR/Cas9 genome editing and human post-mortem studies.


Selvaraj BT et al.
C9ORF72 repeat expansion causes vulnerability of motor neurons to Ca2+-permeable AMPA receptor-mediated excitotoxicity.
Nature Communications
2018 Jan 24

Primary location


Principal Investigator

Other people involved

Prof Siddharthan Chandran

Prof Colin Smith

Dr Matthew Livesey (University of Sheffield)

Dr Jenna Gregory