Neuromuscular Disorders
We work to translate an understanding of the molecular mechanisms of disease at the neuromuscular synapse into treatments. Our work led us to be commissioned to provide a National Advisory and Diagnostic Service for congenital myasthenic syndromes.
Overview
We study diseases that affect neuromuscular transmission, with the major focus on mutations of muscle acetylcholine receptors (AChR) and of proteins that govern synaptic structure.
Research
The neuromuscular synapse is both well understood and accessible for study. Functional analysis of mutations at the molecular level can be directly correlated with measurements of defective synaptic transmission in vivo and with the clinical features of the patients.
The work ranges from the studies of single channels, through to animal models of disease, to phenotypic characterisation of patients. It provides translational research of bedside to bed and back, with the bench research generating data directly relevant to patient treatment regimes. Moreover, a detailed knowledge of inherited dysfunction of neuromuscular transmission forms a paradigm for investigation of other neurological syndromes that may result from defective synaptic transmission in the CNS.
Research projects
- Developing new diagnostic tools for congenital myasthenia
- Using a combination of biochemistry, molecular biology, electrophysiology and advanced microscopy to study the molecular mechanisms underlying disease
- Testing novel therapies for inherited disorders of neuromuscular transmission using transgenic models
Congenital Myasthenia Service
The Congenital Myasthenia Service provides a nationally commissioned specialised service for the diagnosis and management of children and adults in whom a congenital myasthenic syndrome is suspected.
Latest publications
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Structures of the human adult muscle-type nicotinic receptor in resting and desensitized states.
Journal article
Li A. et al, (2025), Cell Rep, 44
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Assessing the Utility of ColabFold and AlphaMissense in Determining Missense Variant Pathogenicity for Congenital Myasthenic Syndromes.
Journal article
Ryan-Phillips F. et al, (2024), Biomedicines, 12
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Congenital myasthenic syndromes: increasingly complex.
Journal article
Ramdas S. et al, (2024), Curr Opin Neurol, 37, 493 - 501
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Congenital myasthenic syndromes.
Journal article
Henehan L. et al, (2024), Pract Neurol, 24, 185 - 187