Postgraduate research opportunities

Novel GPCR interactions as a target for developing new analgesics to treat chronic pain

The aim of this project is first to characterise the physical interaction between P2Y1 and P2Y12 receptors and then to determine how the P2Y1- P2Y12 heterodimer modulates the activity of nerves that sense pain.

Number of places

1

Opens

14 February 2020

Deadline

1 July 2020

Duration

36 Months

Eligibility

Honours degree or equivalent in related subject

 

Project Details

The therapeutic options for treating chronic inflammatory and neuropathic pain are limited (see Burnstock &Kennedy, 2011), but new targets have recently been identified, including P2Y receptors, which are G protein-coupled receptors (GPCR) that are activated by nucleotides, such as ADP (Kennedy et al., 2013; Alexander et al., 2019). P2Y receptors are expressed in pain-sensing C and Ad sensory nerve fibres, so could be targeted to control pain. We showed recently that human P2Y1 and P2Y12 receptors interact to form heterodimers, with novel pharmacological and signalling properties that are different from the individual subtypes (Shakya Shrestha et al., 2010). This is important because it is now recognised that GPCR dimers are common and maybe even crucial for GPCR membrane expression and functional activity (Milligan, 2013). Furthermore, there are clear indications that ADP can act via the P2Y1- P2Y12 heterodimer to modify the activity of pain-sensing nerve fibres. Thus this heterodimer is a novel potential target for the clinical control of pain

During this project you will learn a range of appropriate techniques, including tissue culture, expression of recombinant P2Y receptors, immunoprecipitation, immunohistochemistry, western blotting, confocal microscopy, FRET & BRET imaging analysis and spectrofluorimetric monitoring of intracellular [Ca2+]. These cutting-edge techniques will advance our understanding of how the P2Y1and P2Y12 interact and will help in the search for new, effective analgesics for the treatment of pain disorders.

Funding Details

Applicant will need to self-fund or find sponsorship for tuition and bench fees for duration of studies

Contact us