Unveiling the Journey from Action Potential to Behaviour: Exploring Dopamine and Acetylcholine in Health and Disease. MRC GW4 BioMed DTP PhD studentship for 2026/27 Entry, Department of Clinical and Biomedical Sciences Ref: 5647

Supervisors

Lead Supervisor:  Dr Yanfeng Zhang - University of Exeter - Department of Clinical and Biomedical Sciences 

Co-Supervisor:

Professor Jack Mellor - University of Bristol - School of Physiology, Pharmacology & Neuroscience 

The GW4 BioMed2 MRC DTP is offering up to 17 funded studentships across a range of biomedical disciplines, with a start date of October 2026.

These four-year studentships provide funding for fees and stipend at the rate set by the UK Research Councils, as well as other research training and support costs, and are available to UK and International students.

About the GW4 BioMed2 Doctoral Training Partnership

The partnership brings together the Universities of Bath, Bristol, Cardiff (lead) 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, with opportunities to participate in interdisciplinary and 'team science'. The DTP already has over 90 studentships over 6 cohorts in its first phase, along with 80 students over 4 cohorts in its second phase.

The 122 projects available for application, are aligned to the following themes;

• Infection, Immunity, Antimicrobial Resistance and Repair

• Neuroscience and Mental Health

• Population Health Sciences

Applications open on 1 September 2025 and close at 5.00pm on 20th October 2025.

Please note that we may close the application process before the stated deadline if an unprecedented number of applications are received– check our website for details.

Studentships will be 4 years full time. Part time study may also be available.

Project Information

Research Theme:  Neuroscience & Mental Health

Summary:

How does the brain’s dopamine system drive learning, memory, and motivation? And what goes wrong in diseases like Parkinson’s? This project will explore how dopamine and acetylcholine signals interact to control learning and behaviour, using cutting-edge techniques such as fast-scan cyclic voltammetry, next-generation neurotransmitter imaging, electrophysiology, and computational modelling. You will work at the interface of neuroscience, physiology, and data science to help uncover fundamental brain mechanisms and identify potential therapeutic targets. The project offers excellent training and the chance to contribute to research with real translational impact. 

Description:

Background 

Dopamine plays a central role in learning, motivation, and motor control. Disruption of dopamine signalling underlies conditions such as Parkinson’s disease (PD), where patients experience not only motor deficits but also impairments in learning and decision-making. While the importance of dopamine in brain function is well established, emerging evidence suggests that dopamine’s effects are strongly shaped by its interactions with other neuromodulators, particularly acetylcholine. My recent work (Zhang et al., 2025, Nature Neuroscience) has shown that striatal cholinergic interneurons can dynamically regulate dopamine release at the axonal level, effectively decoupling dopamine neuron firing from dopamine output in target regions. However, the precise mechanisms by which this cholinergic-dopaminergic interplay shapes learning and memory, and how these processes go awry in disease, remain poorly understood. 

Understanding these mechanisms is critical for advancing basic neuroscience and for developing novel treatments for PD and related disorders. This project will use advanced experimental and computational approaches to dissect how cholinergic modulation of dopamine release influences striatal function during learning and decision-making. 

Key research question 

How does cholinergic control of dopamine axonal release influence learning, memory formation, and striatal network activity in health and Parkinsonian conditions? 

Objective 1: Characterise cholinergic control of dopamine release during learning:

• The student will use in vivo fibre photometry or 2 photon imaging to record dopamine and acetylcholine signals in the striatum during behaviour in mice.
• They will assess how cholinergic modulation shapes dopamine dynamics during different stages of Pavlovian and operant conditioning. 

Objective 2: Determine how cholinergic-dopaminergic interactions contribute to striatal microcircuit function:

• The student will perform in vivo recordings (e.g. multiunit recording) to investigate how acetylcholine and dopamine release shape excitability of spiny projection neurons.
• They will explore how these interactions differ across striatal regions in D1 and D2 spiny projection neurons. 

Object 3: Model how cholinergic modulation shapes dopamine- dependent learning:

• The student will use computational modelling, building on reinforcement learning frameworks, to link their experimental data to predictions about behaviour and plasticity.
• The student will be encouraged to integrate their experimental findings into models that can guide further hypotheses and data collection. 

Objective 4: Assess alterations in cholinergic-dopaminergic interactions in Parkinson’s disease models:

• The student will apply these approaches in established mouse models of Parkinson’s disease (e.g. 6-OHDA lesion or transgenic models).
• They will assess whether cholinergic control of dopamine is altered, and whether these changes contribute to behavioural deficits. Opportunities for student ownership and steering This project offers multiple areas where the student can take intellectual ownership and shape the direction of their work. For example:
• The student will have the opportunity to design and refine behavioural tasks to probe specific aspects of learning or motivation relevant to their findings.
• The student will be able to tailor the balance of experimental and computational work based on their interests and strengths. For instance, a student with strong computational skills may wish to develop more sophisticated models of dopamine-acetylcholine interactions, whereas a student more focused on experimental work could prioritise developing novel in vivo recording or manipulation techniques.
• The choice of disease model(s) to study (e.g. acute lesion vs. genetic model) can be adapted based on initial findings and the student’s developing hypotheses.
• The student will be encouraged to present their data at conferences, write manuscripts, and propose follow-up experiments as they gain confidence and expertise. 

Training environment 

The student will be embedded within a vibrant neuroscience research environment at the University of Exeter, with access to cutting-edge facilities for in vivo recording, ex vivo physiology, imaging, and computational support. The supervisory team includes Prof Jack Mellor at the University of Bristol, a leading expert in two-photon imaging of acetylcholine signals in the brain, providing the student with exceptional training in advanced optical approaches. The student will benefit from a multidisciplinary supervisory team and will have the opportunity to work closely with both my national and international collaborators, including Prof Peter Magill at the University of Oxford, Prof Micheal Lin at Stanford University, Prof Alexandre Mourot at Sorbonne University, Dr Mark Howe at Boston University, further broadening their technical expertise and scientific network. This environment will support the development of technical, analytical, and professional skills that will prepare the student for an independent research career. 

Funding

This studentship is funded through GW4BioMed2 MRC Doctoral Training Partnership. It consists of UK tuition fees, as well as a Doctoral Stipend matching UK Research Council National Minimum (£20,780 p.a. for 2025/26, updated each year).

Additional research training and support funding of up to £5,000 per annum is also available.

Eligibility

Residency:

The GW4 BioMed2 MRC DTP studentships are available to UK and International applicants. Following Brexit, the UKRI now classifies EU students as international unless they have rights under the EU Settlement Scheme. The GW4 partners have agreed to cover the difference in costs between home and international tuition fees. This means that international candidates will not be expected to cover this cost and will be fully funded but need to be aware that they will be required to cover the cost of their student visa, healthcare surcharge and other costs of moving to the UK to do a PhD.  All studentships will be competitively awarded and there is a limit to the number of International students that we can accept into our programme (up to 30% cap across our partners per annum).

Academic criteria:

Applicants for a studentship must have obtained, or be about to obtain, a first or upper second-class UK honours degree, or the equivalent qualification gained outside the UK, in an appropriate area of medical sciences, computing, mathematics or the physical sciences.  Applicants with a lower second class will only be considered if they also have a Master’s degree. Please check the entry requirements of the home institution for each project of interest before completing an application. Academic qualifications are considered alongside significant relevant non-academic experience.

English requirements:

If English is not your first language you will need to meet the English language requirements for the University of Exeter by the start of the programme. Please refer to the details in the following web page for further information https://www.exeter.ac.uk/study/englishlanguagerequirements/

Please check the relevant English Language requirements of the university that will host the PhD project.  

Data Protection

If you are applying for a place on a collaborative programme of doctoral training provided by Cardiff University and other universities, research organisations and/or partners please be aware that your personal data will be used and disclosed for the purposes set out below.

Your personal data will always be processed in accordance with the General Data Protection Regulations of 2018. Cardiff University (“University”) will remain a data controller for the personal data it holds, and other universities, research organisations and/or partners (“HEIs”) may also become data controllers for the relevant personal data they receive as a result of their participation in the collaborative programme of doctoral training (“Programme”).

Further Information

For an overview of the MRC GW4 BioMed programme please see the website www.gw4biomed.ac.uk

Entry requirements

Academic Requirements

Applicants for a studentship must have obtained, or be about to obtain, a first or upper second-class UK honours degree, or the equivalent qualification gained outside the UK, in an appropriate area of medical sciences, computing, mathematics or the physical sciences. Applicants with a lower second class will only be considered if they also have a Master’s degree. Please check the entry requirements of the home institution for each project of interest before completing an application. Academic qualifications are considered alongside significant relevant non-academic experience.

English Language Requirements

If English is not your first language you will need to meet the English language requirements for the University of Exeter by the start of the programme. Please refer to the relevant university website for further information.  This will be at least 6.5 in IELTS or an acceptable equivalent.  Please refer to the English Language requirements web page for further information.

Please check the relevant English Language requirements of the university that will host the PhD project. 

How to apply

A list of all the projects and how to apply is available on the DTP’s website at gw4biomed.ac.uk.  You may apply for up to 2 projects and submit one application per candidate only.

Please complete an application to the GW4 BioMed2 MRC DTP for an ‘offer of funding’.  If successful, you will also need to make an application for an 'offer to study' to your chosen institution.

Please complete the online application form linked from our website by 5.00pm on Monday, 20th October 2025.  Please note that we may close the application process before the stated deadline if an unprecedented number of applications are received– check the DTP’s website for details and updates

If you are shortlisted for interview, you will be notified from Tuesday, 23rd December 2025.  Interviews will be held virtually on 27th and 28th January 2026.  

Further Information

For informal enquiries, please contact GW4BioMed@cardiff.ac.uk

For project related queries, please contact the respective supervisors listed on the project descriptions on our website.

Summary