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.
ZFP36-mediated mRNA decay regulates metabolism
Cicchetto AC. et al, (2023), Cell Reports, 42
Recommendations for the development, implementation, and reporting of control interventions in efficacy and mechanistic trials of physical, psychological, and self-management therapies: the CoPPS Statement
Wartolowska K. and FEAKINS K., (2023), British medical journal
Methodological considerations in neuronal extracellular vesicle isolation for α-synuclein biomarkers
Yan S. et al, (2023), Brain
Programmable RNA editing with endogenous ADAR enzymes – a feasible option for the treatment of inherited retinal disease?
Bellingrath J-S. et al, (2023), Frontiers in Molecular Neuroscience, 16