PhD studentship on the Investigation of Cardiac Safety of Illicit Nitazene Opioids

Nitazene opioids are highly potent, synthetic agents that are increasingly used illicitly as recreational drugs. There is mounting concern that increasing illicit nitazene use heralds a new phase of the opioid crisis and may lead to increasing numbers of deaths among users of these drugs. While respiratory depression is a known risk of opioid use, there is relatively little information on other potential adverse effects of nitazenes. Pharmacological inhibition of a potassium (K+) ion channel in the heart called hERG, which plays an important role in cardiac action potential repolarisation, is known to mediate unwanted side effects of diverse non-cardiac drugs that can produce dangerous rhythm disturbances. All new drugs must be tested for the ability to inhibit hERG. However, illicit drugs are not necessarily subject to the careful preclinical studies that new therapeutic agents must undergo. Our pilot data indicate that nitazene drugs have the potential to interact with hERG, suggesting that the heart may be vulnerable to adverse effects of nitazenes. This project aims to determine the extent to which different nitazene drugs inhibit the hERG channel and the mechanisms underlying such interactions. Further, it will investigate whether nitazenes can interact with other key cardiac ion channels and will determine their effects on cardiac action potentials. The project will utilize whole-cell patch-clamp electrophysiological recording from normal and mutant hERG channels and single cell and multicellular recordings from human induced pluripotent stem-cell derived cardiomyocytes to establish the effects of these illicitly used drugs. For recent relevant references from us see PMID: 34727194, PMID: 38143960, PMID: 37122211, PMID: 38326449.

This British Heart Foundation funded 3 year project provides an outstanding opportunity for the successful applicant to receive comprehensive training in a range of research techniques for the study of cardiac safety of drugs. The results of this study will provide increased insight into cardiac risks of an illicit class of drugs, the use of which is increasing and is associated with adverse events. 

The PhD student will join the research teams of Professor Jules Hancox and Dr Steve Harmer and will be based within the excellent research environment in the School of Physiology, Pharmacology and Neuroscience at the University of Bristol.

Candidates will be expected to have at least an upper-second (2.1) class degree or equivalent in a relevant discipline and candidates will be favoured who have an interest in learning electrophysiological, pharmacological and computational methods for ion channel study.

How to apply 

Before applying, please read carefully the information on the prospectus Physiology, Pharmacology and Neuroscience nearmejobs.eu Study at Bristol nearmejobs.eu University of Bristol and make sure you have all the documents listed in the Entry Requirements – Admissions Statement and English Language Requirements.  

To apply, click on the “Apply Now” button and select the programme “Physiology, Pharmacology and Neuroscience (PhD)”. 

Enquiries 

If you have questions about the project, you can contact jules.hancox@bristol.ac.uk and/or s.c.harmer@bristol.ac.uk

If you require assistance with your application, please email fls-pgenquiries@bristol.ac.uk 

Please note that we do not accept applications via email.