Evaluating the role of the cannabinoid receptor, GPR55 in schizophrenia

This project is one of 16 four year PhD Studentships funded by Medical Research Scotland (https://www.medicalresearchscotland.org.uk) to be delivered jointly by the named University and External Partner Organisation (EPO). The Studentship will provide the first-class academic and additional training provided by the EPO needed to equip the successful candidate for a science career in an increasingly competitive market.

"Cannabinoids for the reversal of cognitive impairments in schizophrenia: evaluating the role of the putative, novel cannabinoid receptor GPR55 and the temporoammonic pathway" to be delivered by the University of Dundee [Supervisors: Dr Jenni Harvey and Dr Christopher Henstridge (both Division of Systems Medicine, University of Dundee) and Dr Andrew Irving (School of Biomolecular and Biomedical Science, University College Dublin)] and GW Pharmaceuticals Ltd (https://www.gwpharm.co.uk/) [Company supervisor:Dr Joseph Sutton].

Cognitive dysfunction is a key feature of mental health disorders like schizophrenia. Currently available drugs reduce disease symptoms but have major side effects. Developing new effective drugs relies on identifying agents that restore cognitive function. Clinical evidence suggests cannabinoids, like cannabidiol (CBD), have potential use in schizophrenia as CBD had beneficial effects in recent clinical trials.

CBD is a major active component of cannabis, but as it lacks euphoric activity, it is a promising therapeutic target. But the actions of CBD in the body are highly complex, with reports of activity at classical cannabinoid receptors, but also at the novel cannabinoid receptor, GPR55. Recent evidence suggests that GPR55 is also a novel target for treating disorders like schizophrenia. However, the cellular actions of CBD not well defined, and the role of GPR55 in mediating the anti-psychotic actions of CBD are unclear. Here we propose to address this key gap in our knowledge.

We propose to address the ability of cannabinoids to reverse schizophrenia-related, cognitive deficits in the hippocampus by examining the actions of CBD and selected cannabinoids (provided by GW Pharmaceuticals) on excitatory synaptic transmission in the TA-CA1 pathway. The underlying synaptic mechanisms and pharmacological targets for CBD, in particular GPR55 will be examined. In parallel, we will evaluate the pharmacological profile of neuronal CBD targets in cell-based models. The cellular and subcellular localisation of GPR55 and related targets will be characterised in mouse and post-mortem human tissue from schizophrenic patients, using state-of-the-art in-situ hybridisation technology and high-resolution imaging approaches.

ENQUIRIES:
Enquiries should be sent by email to Dr Jenni Harvey:
[Email Address Removed]

APPLICATIONS:
Applicants must have obtained, or expect to obtain, a first or 2.1 UK honours degree, or equivalent for degrees obtained outside the UK, in a relevant biomedical science discipline.

Applicants should send a CV, the contact details of 2 referees (including email addresses) and a covering letter, explaining why the applicant wishes to carry out this project, by email to Dr Jenni Harvey:
[Email Address Removed]

Please note, your application may be shared with the funders of this PhD Studentship, Medical Research Scotland and GW Pharmaceuticals Ltd.

Interviews are expected to take place 3-4 weeks after the closing date for applications. In light of the current coronavirus situation, interviews may be conducted by video conference.

It is anticipated that the PhD Studentship will start in October 2020.