This opportunity is now closed.

Funded PhD Opportunity

Development of a pharmacogenomic model to predict efficacy or adverse events to cannabidiol treatment of arthritic pain.

Subject: Biomedical Sciences


Summary

The endogenous cannabinoid system modulates neuronal and immune cell function, both of which play key roles in Osteoarthritis (OA) and rheumatoid arthritis (RA) pain. Cannabidiol (CBD) is a non-psychoactive compound extracted from cannabis. CBD binding of endogenous receptors can produce reliable anti-nociceptive effects in preclinical inflammatory and neuropathic pain models. However cannabidiol’s safety and efficacy have not yet been studied independently by clinical trial for pain in arthritis. The ESCAPe (CHITIN) study proposed would be the first of its kind to investigate the safety profile and pain effects of CBD, in these conditions. CBD is metabolized in the liver by cytochrome P450 enzymes CYP2C and CYP3A converting it into 7-OH-CBD and 6-OH-CBD.

Of particular relevance to safety, CBD has potential to block cytochrome P450 metabolism of other co-medications in the liver, such as NSAID and opioid co-medications in arthritis patients. Therefore pharmacogenomic and pharmacokinetic studies will be conducted in parallel, to identify variants of cannabidiol metabolising enzymes and receptors which in combination could be carried by individuals more likely to respond or at higher risk of adverse events.

Aim: Discover genomic variant data that to stratify patients achieving pain reduction or at risk of adverse events, when treated with cannabidiol.

Objectives:

1. Perform pharmacokinetic analysis of CBD, NSAID and opioid metabolites in patients to measure any changes in metabolism attributable to CBD.

2. Data from a pharmacogenomic screen of CBD metabolising enzymes will be analysed for associations with CBD reduction in pain scores or adverse events.

Methods:

a)Genomic analyses: DNA will be extracted from whole blood samples and targeted gene sequencing and variant calling will performed using TruSeq custom amplicon kits and an Illumina MiSeq instrument at NI Centre for Stratified Medicine (NICSM).  Analysis of single nucleotide polymorphisms (SNPs) with functional consequences for CBD metabolism or signalling will be focussed on CYP2C19 and CYP3A4 genes. The strength of associations between individual SNPs and drug levels or pain response scores will be assessed by multivariate regression modelling.

b)Pharmacokinetics: the metabolism of CBD and its metabolites will be analysed in blood plasma and urine samples for both Stage 1 and 2 studies. Samples will be centrifuged to remove cellular material and frozen at the recruitment site, sent to NICSM for analyses at the Mass Spectrometry Core Technology Unit at Ulster University. CBD, 7-OH-CBD and 6-OH-CBD, NSAID and opioid plasma and urine concentrations will be ascertained by a liquid extraction surface analysis (LESA)-nano electrospray ionisation triple quadrupole mass spectrometry method (ESI-QQQ MS) using.

c)Bioinformatic analyses:  Statistical analysis will be performed by SPSS (version 24.0). Pre- and post-treatment outcome data will be will be analysed to examine any relationships between the specific genotype/drug meatbolite profile of a patient with their disease activity, demographics and clinically determined response to therapy. A patient stratification algorithm and model will be designed to detect associations between specific gene variants CBD pain response or adverse event.


Essential criteria

  • Upper Second Class Honours (2:1) Degree or equivalent from a UK institution (or overseas award deemed to be equivalent via UK NARIC)
  • Sound understanding of subject area as evidenced by a comprehensive research proposal
  • A comprehensive and articulate personal statement

Desirable Criteria

If the University receives a large number of applicants for the project, the following desirable criteria may be applied to shortlist applicants for interview.

  • First Class Honours (1st) Degree
  • Masters at 65%
  • Completion of Masters at a level equivalent to commendation or distinction at Ulster
  • Research project completion within taught Masters degree or MRES
  • Experience using research methods or other approaches relevant to the subject domain
  • Work experience relevant to the proposed project
  • Publications - peer-reviewed
  • Experience of presentation of research findings

Funding

    The University offers the following awards to support PhD study and applications are invited from UK, EU and overseas for the following levels of support:

    Vice Chancellors Research Studentship (VCRS)

    Full award (full-time PhD fees + DfE level of maintenance grant + RTSG for 3 years).

    This scholarship will cover full-time PhD tuition fees and provide the recipient with £15,000 maintenance grant per annum for three years (subject to satisfactory academic performance). This scholarship also comes with £900 per annum for three years as a research training studentship grant (RTSG) allocation to help support the PhD researcher.

    Vice-Chancellor’s Research Bursary (VCRB)

    Part award (full-time PhD fees + 50% DfE level of maintenance grant + RTSG for 3 years).

    This scholarship will cover full-time PhD tuition fees and provide the recipient with £7,500 maintenance grant per annum for three years (subject to satisfactory academic performance). This scholarship also comes with £900 per annum for three years as a research training studentship grant (RTSG) allocation to help support the PhD researcher.

    Vice-Chancellor’s Research Fees Bursary (VCRFB)

    Fees only award (PhD fees + RTSG for 3 years).

    This scholarship will cover full-time PhD tuition fees for three years (subject to satisfactory academic performance). This scholarship also comes with £900 per annum for three years as a research training studentship grant (RTSG) allocation to help support the PhD researcher.

    Department for the Economy (DFE)

    The scholarship will cover tuition fees at the Home rate and a maintenance allowance of £ 15,009 per annum for three years. EU applicants will only be eligible for the fee’s component of the studentship (no maintenance award is provided). For Non-EU nationals the candidate must be "settled" in the UK. This scholarship also comes with £900 per annum for three years as a research training studentship grant (RTSG) allocation to help support the PhD researcher.

    Due consideration should be given to financing your studies; for further information on cost of living etc. please refer to: www.ulster.ac.uk/doctoralcollege/postgraduate-research/fees-and-funding/financing-your-studies


Other information


The Doctoral College at Ulster University


Reviews

My experience has been great and the people that I have worked with have been amazing

Kieran O'Donnell - 3D printing of biological cells for tissue engineering applications

Watch Video  

Completing the MRes provided me with a lot of different skills, particularly in research methods and lab skills.

Michelle Clements Clements - MRes - Life and Health Sciences

Watch Video  

Throughout my PhD I’ve been provided with continuous support and guidance by my supervisors and the staff at the University.I’ve also received many opportunities to further enhance my professional development in the form of teaching experience and presenting my work at conferences which will aid in my pursuit of a career in academia or industry.

William Crowe


Key dates

Submission deadline
Monday 19 February 2018

Interview Date
6, 7 and 8 March 2018


Applying

Apply Online  


Contact supervisor

Dr David Gibson


Other supervisors

Related Funded Opportunities

Diabetes

Subject: Biomedical Sciences

 View details

Genomic Medicine

Subject: Biomedical Sciences

 View details

The regulation of rhamnolipid biosynthesis in Burkholderia thailandensis.

Closing date:
Tuesday 1 September 2020
Subject: Biomedical Sciences

 View details

Stratified Medicine

Subject: Biomedical Sciences

 View details

Optometry and Vision Science

Subject: Biomedical Sciences

 View details

MRes in Biomedical Sciences

Subject: Biomedical Sciences

 View details

The production of rhamnolipid biosurfactant by Pseudomonas aeruginosa growing in biofilms.

Closing date:
Tuesday 1 September 2020
Subject: Biomedical Sciences

 View details

Molecular Pathology of Glaucoma

Closing date:
Wednesday 1 January 2020
Subject: Biomedical Sciences

 View details

The design and analysis of a novel photo-activated antimicrobial system

Closing date:
Tuesday 1 September 2020
Subject: Biomedical Sciences

 View details