Unlocking a new neuroimmune strategy to treat Alzheimer’s disease. MRC GW4 BioMed DTP PhD studentship for 2026/27 Entry, Department of Clinical and Biomedical Sciences Ref: 5645

Supervisors

Lead Supervisor:  Dr Jonathan Witton - University of Exeter - Department of Clinical and Biomedical Sciences 

Co-Supervisors:

Dr Valentina Mosienko - University of Bristol - School of Physiology, Pharmacology and Neuroscience 

Professor Wendy Noble  - University of Exeter - Department of Clinical and Biomedical Sciences 

Professor Jonathan Brown - University of Exeter - Department of Clinical and Biomedical Sciences 

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:

Microglia are the brain’s resident immune cells. The latest research suggests that, alongside conventional molecular signals, microglia function is also influenced by certain patterns of brain activity. Our team has found that a type of brain activity linked to cognition – called gamma oscillations – can regulate microglia through a particular receptor subtype, potentially triggering a neuroprotective response (DOI: bioRxiv 10.1101/2025.03.03.641001). Using a novel experimental assay developed by our lab, this project will uncover how this brain-immune signalling works to identify new therapeutic targets for Alzheimer’s disease and other neurological disorders involving malfunction of the brain’s immune system. 

Description:

BACKGROUND 

Microglia are brain-resident immune cells that provide the main form of defence against neuropathology. It is well known that dynamic crosstalk between microglia and neuronal cells maintains brain homeostasis and coordinates neuroimmune responses. Recent studies, however, have identified a new form of neuron-microglia communication driven by rhythmic neuronal activity. Communication between neurons generates rhythmic patterns of electrical brain activity, known as neuronal oscillations. Studies have revealed that neuronal oscillations around 40 Hz – called gamma oscillations – generate a signal that regulates microglia function (PMID: 31076275). Specifically, gamma oscillations promote a homeostatic and neuroprotective microglial response linked to enhanced surveillance and phagocytosis that can clear pathological proteins (such as amyloid-β) in mouse models of Alzheimer’s disease (AD) (PMID: 27929004). This is important because impaired gamma activity and microglial dysfunction are hallmark features of neurodegenerative diseases like AD, thereby raising the tantalising possibility that these diseases could be treated by triggering Gamma- Activity Induced Neuron-microglia Signalling (hereinafter, GAINS). 

However, very little is known about how GAINS works due to a lack of tractable models of this phenomenon. To address this, we have developed a novel model of GAINS in ex vivo mouse brain slices and have used it to discover that GAINS operates through colony stimulating factor 1 receptors (CSF1Rs), which are expressed by microglia, and via nuclear factor kappa B (NFκB) pathway signalling (DOI: bioRxiv 10.1101/2025.03.01.641001). Excitingly, molecular targets of CSF1Rs and NFκB intersect with signalling pathways linked to AD risk genes (PMID: 24951455, PMID: 29312321), resilience to disease (PMID: 40311610), and targets of AD medicines in clinical trial (e.g. NCT05744401), highlighting the translational potential of this research. 

QUESTION & AIMS 

The scientific question at the heart of this project is: What are the specific cellular and molecular mechanisms by which gamma-frequency neuronal activity modulates microglial function? Building on our recent findings (DOI: bioRxiv 10.1101/2025.03.01.641001), we hypothesise that GAINS is mediated by factors downstream of microglial CSF1Rs that converge on NFκB pathway activation. Objectives to test this hypothesis are: 

1. Define molecular mediators of GAINS downstream of CSF1R signalling ex vivo.
2. Validate the role of candidate mediators of GAINS in vivo.
3. Explore the role of astrocytes as a source of gamma activity- evoked CSF1 and their contribution to GAINS. 

PROJECT DESIGN 

Objective 1 will be tackled using an established ex vivo GAINS model developed by our lab. Gamma oscillations will be induced in mouse brain slices using pharmacology and optogenetic techniques and monitored using electrophysiology, while the responses of fluorescence-tagged microglia (labelled using Alexa 488 isolectin B4) are measured using 2- photon microscopy (e.g. changes in morphology, density, motility). To dissect the intracellular pathways linking CSF1R activation to NFκB, we will apply well-validated, selective pharmacological inhibitors targeting candidate molecular cascades, including MAP kinase-ERK, protein kinase C, and PI3 kinase-Akt (PMID: 35290551). 

For Objective 2, we will confirm the relevance of CSF1Rs and their downstream molecular targets in GAINS in vivo. We will induce gamma oscillations in mice using optogenetics (mirroring our slice model) and via patterned 40 Hz visual stimulation known to evoke GAINS in visual cortex (PMID: 3106275). Mice will be treated with CSF1R antagonists (e.g. BLZ945) or inhibitors of their targets that block GAINS ex vivo (i.e. in Objective 1). We will also employ acute in vivo 2-photon brain imaging in mice to visualise microglia dynamics (e.g. motility, migration) during GAINS and where it is pharmacologically blocked. 

Astrocytes are a key source of CSF1 in the brain (PMID: 34472465), making them prime candidates as an upstream regulator of GAINS. Objective 3 will leverage our ex vivo assay to test the role of astrocytes in GAINS. Specifically, we will disrupt astrocyte function during GAINS in brain slices using pharmacological inhibitors of astrocyte metabolism (e.g. aminoadipic acid) or viral-genetic tools currently employed by co- supervisor Mosienko. 

STUDENT OWNERSHIP 

Our project objectives are complementary rather than sequential, meaning different research strands can run in parallel and be tailored to the student’s interests. As the project incorporates both ex vivo (Objectives 1 & 3) and in vivo (Objective 2) models, the student can choose to emphasise one or both approaches depending on their preferences. Similarly, the student can balance the focus between cellular/molecular signalling (Objectives 1 & 2) and astrocyte-focused (Objective 3) experiments in line with their interests. Additionally, while not an explicit focus, co-supervisors Mosienko and Noble bring extensive molecular biology expertise, which offers opportunities to explore GAINS-related changes in gene and/or protein expression in microglia and astrocytes. This direction can also be supported by our team’s active collaborations with Exeter’s Complex Disease Epigenomics Group (https://www.epigenomicslab.com/), should the student wish to develop skills in this area. 

OUTCOMES 

The project will uncover cellular and molecular mechanisms underlying a novel neuroimmune pathway that could be leveraged to treat neurodegenerative disorders characterised by aberrant gamma activity and disrupted neuroimmune function, such as AD.

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