Pathophysiological disease mechanisms underlying motor neuron dysfunction in MND

About the project

Research in the Miles lab aims to reveal novel pathophysiological mechanisms that underlie motor neuron dysfunction and eventual degeneration in MND. We are currently utilising a combination of electrophysiological and anatomical analyses applied to animal and human stem cell-based models to investigate deleterious interactions between glial cells and motor neurons, perturbations in synaptic connectivity, and changes in ion channel function that effect motor neuron excitability.

We hope to reveal novel therapeutic targets for the development of much-needed treatment strategies aiming to improve motor neuron function and survival in MND.


MND Association, MND Scotland


Broadhead MJ, Doucet K, Kantelberg OG, Zhu F, Grant SGN, Horrocks MH, Miles GB
Synaptic expression of TAR-DNA-binding protein 43 in the mouse spinal cord determined using super-resolution microscopy
Frontiers in Molecular Neuroscience. 2023. 16:1027898
McIntosh J, Mekrouda I, Dashti M, Giuraniuc C, Banks RW, Miles GB, Bewick GS
Development of abnormalities at the neuromuscular junction in the SOD1-G93A mouse model of ALS: dysfunction then disruption of postsynaptic structure precede motor symptoms.
Frontiers in Molecular Neuroscience. 2023. 16:1169075.
Broadhead MJ, Bonthron C, Waddington J, Smith W V, Lopez MF, Burley S, Valli J, Zhu F, Komiyama NH, Smith C, Grant SGN, Miles GB
Selective vulnerability of tripartite synapses in amyotrophic lateral sclerosis.
Acta Neuropathologica. 2022. 143:471–486
Zhao C, Devlin AC, Chouhan AK, Selvaraj BT, Stavrou M, Burr K, Brivio V, He X, Mehta AR, Story D, Shaw CE, Dando O, Hardingham GE, Miles GB, Chandran S
Mutant C9orf72 human iPSC-derived astrocytes cause non-cell autonomous motor neuron pathophysiology.
Glia. 2020. 68(5):1046-1064
Devlin AC, Burr K, Borooah S, Foster JD, Cleary EM, Geti I, Vallier L, Shaw CE, Chandran S, Miles GB
Human iPSC-derived motoneurons harbouring TARDBP or C9ORF72 ALS mutations are dysfunctional despite maintaining viability
Nat Commun. 2015 Jan 12;6:5999

Primary location

St Andrews

Principal Investigator

Other people involved

Key collaborators: Siddharthan Chandran, Guy Bewick