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.
Available Student Projects
- Develop a positive allosteric modulator of skeletal muscle nicotinic acetylcholine receptor
- Study the ultrastructure of the neuromuscular junction using FIB milling and cryo electron tomorgraphy
Research projects
- Searching for new genes associated with the congenital myasthenic syndromes using next generation sequencing
- 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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Can AlphaFold's breakthrough in protein structure help decode the fundamental principles of adaptive cellular immunity?
Journal article
McMaster B. et al, (2024), Nat Methods
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Reassessing the association: evaluation of a polyalanine deletion variant of RUNX2 in non-syndromic sagittal and metopic craniosynostosis
Journal article
Walton I. et al, (2024), Journal of Anatomy
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Genome engineering with Cas9 and AAV repair templates generates frequent concatemeric insertions of viral vectors.
Journal article
Suchy FP. et al, (2024), Nat Biotechnol
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Chromatin and aberrant enhancer activity in KMT2A rearranged acute lymphoblastic leukemia.
Journal article
Milne TA., (2024), Curr Opin Genet Dev, 86