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.
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.
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
- 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.
New analysis of atypical spermatocytic tumours reveals extensive heterogeneity and plasticity of germ cell tumours†
Rajpert‐De Meyts E. et al, (2024), The Journal of Pathology
Ultrahigh frequencies of peripherally matured LGI1- and CASPR2-reactive B cells characterize the cerebrospinal fluid in autoimmune encephalitis
Theorell J. et al, (2024), Proceedings of the National Academy of Sciences, 121
Antibody agonists trigger immune receptor signaling through local exclusion of receptor-type protein tyrosine phosphatases.
Lippert AH. et al, (2024), Immunity, 57, 256 - 270.e10
Homozygous SMAD6 variants in two unrelated patients with craniosynostosis and radioulnar synostosis.
Luyckx I. et al, (2024), J Med Genet