We are pleased to offer a 3 year, fully-funded, PhD studentship to study synthetic cannabinoids and their metabolites within a supportive, dynamic and impactful research team.
The project is based primarily at the Leverhulme Research Centre for Forensic Science, University of Dundee United Kingdom, but includes funded research placements at Linköping University, Sweden. The supervisory team, comprising Dr. Craig McKenzie (Dundee), Professor Ulrich Zachariae (Dundee) and Professor Henrik Gréen (Linköping), is highly experienced in illicit drug and new psychoactive substances (NPS) research, and in the study of drug-receptor interactions.
About the project
Synthetic cannabinoids (SCs) are a structurally diverse group of NPS, with substances of variable potency and efficacy emerging constantly on the global illicit drugs market. SCs have been implicated in non-fatal poisonings and drug-related deaths worldwide. Once consumed (normally by smoking or vaping), a large proportion of the SCs will bind to plasma proteins and the bound and unbound fraction will be transported via the circulatory system to biological receptors controlling psychoactive and physiological effects. Unbound SCs are metabolised relatively rapidly and the parent drug and its metabolites are excreted to varying extents. The structural and physicochemical properties of the parent SCRAs and their metabolites determine their metabolic stability, toxicology, pharmacokinetics and pharmacology and influence drug detection time windows in biological tissues relevant to toxicological investigations.
Unbound SCs bind to and activate cannabinoid (CB1 and CB2) G-protein coupled receptors (GPCRs). SCs elicit a range of psychoactive and physiological effects via these and other biological targets. Such SC-CB receptor interactions can be studied using both laboratory-based (in vitro) and computational (in silico) techniques. SCs which bind to and activate cannabinoid receptors are referred to as synthetic cannabinoid receptor agonists (SCRAs). SCRAs interact with chemical residues within the receptor binding pocket eliciting a conformational change in the receptor, facilitating a transfer of information from the outside of the cell to the inside, eliciting a downstream physiological response.
The objectives of this study include:
(i) synthesis of relevant reference standards for emerging and ‘prophetic’ SCRAs and their metabolites;
(ii) experimental determination of relevant physicochemical and toxicological properties of SCRAs and their metabolites;
(iii) conduct of in vitro pharmacokinetics studies to estimate in vivo drug behaviour and relevance of metabolite-CB1 receptor activation to drug effects;
(iv) conduct of in vitro receptor binding and activation studies;
(v) application of computational methods to study SCRAs and SCRA metabolite interactions with the CB1 receptor.
The successful candidate will receive relevant training in fundamental pharmacological research methodology; in synthetic cannabinoid and synthetic cannabinoid metabolite reference standard synthesis; the use and application of tandem mass spectrometry and high-resolution accurate mass spectrometry (HRAM) for drug detection and toxicology; training in in vitro techniques to study SCRA pharmacokinetics and pharmacology; and in computational methods to study SCRA/CB1 receptor interactions. The successful candidate will be encouraged to enhance their professional training through interaction with professional bodies such as the Royal Society of Chemistry (RSC), Chartered Society of Forensic Science (CSoFS), and The International Association of Forensic Toxicologists (TIAFT).
Person Specification
Applicants should have a minimum of a 2:1 honours degree [preference for 1st class honours]; or a Masters (preference for Merit or above), or equivalent GPA from non-UK universities, in a relevant subject area, e.g. organic synthesis, pharmaceutical chemistry, drug discovery, pharmacology, chemistry, analytical chemistry, forensic chemistry, computational chemistry (the latter with relevant laboratory experience) or equivalent. PhD candidates are required to be creative, well organized, fluent in English writing and have good oral communication skills. The successful candidate will receive extensive additional training in these areas as part of their researcher training.
Application process
Applicants must provide a CV, a copy of relevant degree certificates and transcripts, and a covering letter (up to 1000 words maximum) detailing why you are interested in this PhD to [Email Address Removed] by the 18th February 2020. Your cover letter should provide a summary of the relevant experience you can bring to this project and of your understanding of this subject area with relevant references. Contact details for two referees should also be provided in the cover letter. Informal enquiries can be made by contacting Dr. Craig McKenzie ([Email Address Removed]). The successful candidate will be required to complete the full university admission process once selected.
Continue with Facebook
