Declan Manning

University of Liverpool


Dr Carline Dart and Dr Richard Evans

I studied my BSc in Pharmacology at The University of Manchester, with industrial experience with the MRC Unit in The Gambia. I am interested in cell signalling, specifically the function of membrane proteins such as GPCRs and more recently, Ca2+-conducting ion channels in cell physiology. The pharmacology of membrane-bound receptors and ion channels forms an essential component of pharmaceutical design and our understanding of the signalling patterns they are involved in may drive significant future drug design. This is why I am interested to study the unknown mechanisms through which membrane protein facilitate intracellular events in response to a range of intra- and extra-cellular stimuli.

Biophysical and molecular characterisation of Orai channels in skin cell lines 

As part of my Unilever-sponsored CASE project, I am conducting an in vitro investigation into the activity of Orai channels in skin cell lines. Orai channels conduct an inward flow of Ca2+ ions in response to depletion of endoplasmic reticulum Ca2+ stores, allowing the cell to replenish stores and maintain various cellular functions. This current (ICRAC) also plays a signalling role: in eccrine sweat gland clear cells, this signal leads to sweat secretion; in keratinocytes, this signals contributes to cell differentiation processes.

My project involves characterisation of the store-operated Ca2+ entry processes of representative skin cell lines, examining presence of Orai channel and activating stromal interaction molecule (STIM) subtypes at the RNA and protein level. Functionally, the activity of Orai channels can be visualised through Ca2+-imaging, whilst patch clamp electrophysiology allows us to examine in exquisite detail the activation and inactivation of these channels, under physiological conditions and under the effects of bioactive compounds.

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