GW4 BioMed2 MRC DTP PhD project: Synthetic heroin: understanding the dangers of nitazene drugs

This project is one of a number that are in competition for funding from the GW4 BioMed2 MRC Doctoral Training Partnership which is offering up to 21 studentships for entry in September 2025.

The DTP brings together the Universities of Bath, Bristol, Cardiff and Exeter to develop the next generation of biomedical researchers. Students will have access to the combined research strengths, training expertise and resources of the four research-intensive universities. More information may be found on the DTP’s website.

Supervisory Team:

Dr Chris Bailey, University of Bath, Department of Life Sciences ([email protected])

Professor Eamonn Kelly, University of Bristol, School of Physiology, Pharmacology and Neuroscience

Dr Robin Corey, University of Bristol, School of Physiology, Pharmacology and Neuroscience

The Project:

Drug-related deaths are now at the highest ever recorded in the UK. In 2020 there were nearly 1,200 drug overdose deaths, the majority of which were opioid overdoses. Opioid drugs, such as heroin, act on mu opioid receptors (MOPrs). MOPrs are widely expressed in the brain and, when activated, can cause analgesia, euphoria, and respiratory depression.

Historically, heroin has been the most widely used opioid drug on the street. However, there has been a recent rise in the availability of synthetic opioids, particularly the class of drug known as ‘nitazenes’. These have already been the cause of fatal overdoses and their use is predicted to rapidly rise [1], potentially leading to future public health crises. However, the pharmacology of nitazenes is poorly understood: how they interact with MOPrs, and what the implications are for risk of overdose and treatment of overdoses.

This project aims to investigate the neuropharmacology of nitazenes using an interdisciplinary approach. The supervisory group will consist of 3 academics: Chris Bailey (Bath), Eamonn Kelly (Bristol) and Robin Corey (Bristol) with complementary expertise in a range of in silico, in vitro, ex vivo and in vivo techniques to investigate the actions of nitazenes at a receptor, cellular and system level.

Conventionally, agonists at receptors were thought to differ only in terms of their affinity (how well they bind to the receptor) and their efficacy (how well they activate the receptor). Recently, we have shown that the effects of different agonists at opioid receptors can also depend on how they bind to the receptor [2], and whether the cell is depolarized or not [3]. Further, MOPrs are present in neurons both presynaptically (on nerve terminals) and postsynaptically (on cell bodies and dendrites). We have preliminary evidence that different agonists can preferentially signal through presynaptic receptors, due to presynaptic receptors being more mobile than postsynaptic receptors [4]. And other studies have shown that the specific G-protein signalling induced by different agonists can affect pre- vs. post-synaptic signalling [5]. This pre/post-synaptic ‘bias’ can have profound effects on their effects in the whole animal [5, 6].

This project will focus on determining the pharmacodynamic characteristics of nitazenes by using brain slice electrophysiology to determine their actions and presynaptic and postsynaptic MOPrs, in neurons responsible for the rewarding and respiratory depressant effects of opioids [7]. Additional insight will be gathered using in silico molecular dynamics studies [2, 8] and in vitro cell-based signalling assays [9] with the PIs in Bristol. Further, the effects of nitazenes in the whole animal will be assessed using in vivo behavioural assays of reward/addiction and respiratory depression [10, 11]

This project will give the student high-quality training in a broad range of techniques, all aiming to provide a comprehensive assessment of nitazenes at the receptor, cellular and whole-animal level. The ultimate goal will be to understand their relative harms and inform novel approaches to decrease those harms.

Requirements:

Applicants must have obtained, or be expected to obtain, a First or Upper Second Class UK Honours degree, or the equivalent qualifications gained outside the UK, in an area appropriate to the skills requirements of the project. Applicants with a lower second class will only be considered if they also have a Master’s degree. Academic qualifications are considered alongside significant relevant non-academic experience.

Non-UK applicants will also be required to have met the English language entry requirements of the University of Bath.

Enquiries and Applications:

Informal enquiries are welcomed and should be directed to Dr Chris Bailey – [email protected]

Formal applications must be submitted direct to the GW4 BioMed2 DTP using their online application form: GW4 BioMed MRC DTP – GW4 BioMed MRC DTP

A list of all available projects and guidance on how to apply may be found on the DTP’s website. You may apply for up to 2 projects.

APPLICATIONS CLOSE AT 17:00 (GMT) ON 4 NOVEMBER 2025.

IMPORTANT: You do NOT need to apply to the University of Bath at this stage – only those applicants who are successful in obtaining an offer of funding from the DTP will be required to submit an application for an offer of study from Bath.