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Voltage-gated potassium channels as therapeutic targets for treatment of chronic pain

Project Description

There is currently a large unmet need for new and safe therapies to treat chronic pain, as emphasized by the recent press coverage of the “opioid epidemic” in the US, where the use of opioid analgesics for treatment of pain have led to widespread addiction and drug abuse. Pharmacological openers of voltage-gated potassium channels in neurons provide an ideal mechanism for reducing neuronal excitability and treating diseases associated with hyperexcitability. For example, Kv7 openers, flupirtine and retigabine, have been used successfully in the clinic for treatment of epilepsy and pain.

Kv2 channels have unique properties compared to other potassium channels where they control neuronal excitability and also forms clusters at the cell membrane. These clusters are sites of vesicle exocytosis and secretion. Kv2 channels assembled with Kv9.1 (Kcns1) have been shown to have a a key role in pain processing by controlling the excitability of peripheral sensory neuron (Costigan et al. 2010 Brain 133:2519-27; Tsantoulas et al. 2012 J Neurosci 32:17502–13; Tsantoulas et al. 2018 Pain 159:1641-1651). Development of selective Kv2/Kv9.1 openers could provide a new generation of safe non-opioid analgaesics.

The project will have two main aims: first to characterize the effect of the Kv9.1 subunit on the properties of the Kv2.1 channel and second to identify novel Kv2.1/Kv9.1 channel openers. Conductance and non-conductance properties of these channels will be examined. A range of molecular and cell biologial techniques will be used, including fluorescence microscopy (confocal and TIRF), protein biochemistry and electrophysiology.
The successful candidate will join a team of researchers working in the Sussex Drug Discovery Centre and in Neuroscience. The diverse array of expertise within this group provides an excellent opportunity for a PhD student to learn multiple techniques and to become familiar with the process of drug discovery in an academic environment, whilst also working closely with researchers who have considerable industry experience.

Funding Notes

This funded position, which covers fees and a stipend at standard RCUK rates, is open to Home / EU applicants.

Ideal candidates will have a strong background in Neuroscience and/or Biomedical Science with an interest in the molecular basis of chronic pain and in the development of novel analgesics. Eligible candidates will have recently received an MSc and/or a First or high 2:1 BSc in a relevant subject. Candidates for whom English is not their first language will require an IELTS score of 6.5 overall, with not less than 6.0 in any section.

Related Subjects

How good is research at University of Sussex in Biological Sciences?

FTE Category A staff submitted: 47.61

Research output data provided by the Research Excellence Framework (REF)

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