Molecular Mechanisms of Receptor and Ion Channel Regulation in Pain and Inflammation

"Receptors and ion channels are responsible for the transmission of signals across cellular membranes that regulate a plethora of biological and cellular functions. The molecular mechanisms that regulate receptors and ion channels and their downstream signaling pathways in the cardiovascular and nervous systems are complex. Whereas receptors and ion channels were originally thought to act as single entities, it is now clear that protein•protein interactions, protein trafficking and sequestration and receptor co-operativity expand the repertoire of signaling cascades that can be elicited by a single agonist. The phenomenon of biased agonism (sometimes called ‘functional selectivity’) also adds further to this complexity. Our work is primarily focused on G protein-coupled receptors, toll-like receptors and ion channels involved in the transmission of pain and inflammatory processes and investigates how molecular and cellular mechanisms regulate signal transduction and contribute to normal physiological processes and promote disease.
Studies will provide will provide specialist training in state-of-the-art molecular, biochemical, pharmacological, microscopic and genetic tools to discover new targets for the treatment of pain and inflammatory processes that can be associated with many human disorders including migraine, asthma and inflammatory bowel disease.

• Methods include:
o Cell culture of cell lines
o Plasmid transfections, viral transductions
o Immunocytochemistry/immunohistochemistry
o Western blotting
o Confocal laser scanning microscopy
o FRET/BRET-based signaling assays
o Ca2+-signaling assays
o Plasmid DNA cloning, RT-PCR, qPCR
o Gene editing e.g., CRISPR/Cas9
o Cell-based assays e.g. viability and proliferation assays
o Gene reporter assays e.g., Luciferase assays

Key words: GPCRs, Ion channels, Signaling, Trafficking, Pain, Inflammation.

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