SLMS Academic Careers Office

Grand Challenges

25. Calcium channel trafficking, nociceptive neurotransmission and mechanism of action of gabapentinoid drugs in mouse models of neuropathic pain

Supervisor Pair: Professor Annette Dolphin and Professor John Wood
Potential Student’s Home Department: Neuroscience, Physiology and Pharmacology 

Chronic neuropathic pain results from damage to the peripheral somatosensory dorsal root ganglion (DRG) neurons   One of the genes whose expression is up-regulated and is involved in the development of neuropathic pain is Cacna2d1, encoding the auxiliary calcium channel subunit α2δ-1, which is important for calcium channel trafficking.  N-type calcium channels (molecular name CaV2.2) are the main calcium channel isoform involved in synaptic transmission in DRG neurons.  We will investigate the hypothesis that the trafficking of CaV2.2 to presynaptic terminals is altered by the up-regulation of α2δ-1 that occurs following the development of neuropathic pain.  This project will examine CaV2.2 trafficking using CaV2.2 constructs which we have engineered to have a tag in an extracellular loop.  Experiments will be performed both in vitro and in vivo.

The primary supervisor, Professor Annette Dolphin is an expert in voltage gated calcium channels, in terms of their trafficking, function and interaction with other proteins.  She also has a strong interest in how these channels contribute to experimental models of neuropathic pain, and has published extensively on this.

Professor John Wood is one of the acknowledged world experts in dissecting the molecular mechanisms involved in nociception by the use of mice in which specific ion channels, particularly voltage-gated sodium channels, have been knocked out in particular subsets of DRG neurons. He is also an expert in behavioural assessment of nociception, using a variety of neuropathic pain models.

The student will therefore have access to all the behavioural and mouse model expertise in John Wood’s lab, and the biochemical, imaging and electrophysiological expertise relating to understanding calcium channel function in Annette Dolphin’s laboratory.