Exploring the role of bacterial infections in modulating the gut–brain–microbiome axis in Alzheimer’s disease

About the Project

Applications are invited for a self-funded, 3 year full-time or 6 year part-time PhD project.

The PhD will be based in the School of Medicine, Pharmacy and Biomedical Sciences and will be supervised by Dr Murphy Wan.

The work on this project will:

• Investigate how overexpression of APP and accumulation of Aβ modulate the composition of the gut microbiota and associated immune responses
• Explore if, and how, a gut-associated bacterial infection contributes to AD progression via the gut-brain axis

Alzheimer’s disease (AD) remains one of the world’s most pressing health challenges. While current therapeutic strategies primarily focus on targeting amyloid β (Aβ) accumulation in the brain, their clinical benefits are limited, indicating that additional biological pathways likely contribute to disease onset and progression. Emerging research highlights a pivotal role for the immune system and the gut–brain–microbiome axis in modulating AD pathology.

The gut microbiota and their metabolites can profoundly influence brain function, neuroinflammation, and overall disease progression. Disruptions to gut microbiota composition and impaired gut-brain communication are increasingly recognised as contributing factors in AD pathogenesis; however, the underlying mechanisms remain poorly understood.

This project will build upon promising findings generated in our lab, supported by an Alzheimer’s Research UK pump-priming grant, which suggests that Aβ may modulate the gut–brain–microbiome axis, thereby affecting disease progression.

The project also offers flexibility to tailor specific research questions based on the successful candidate’s interests and background. Following consultation, we will collaboratively design a suite of experimental approaches to address the agreed focus areas. Complementary studies may be incorporated, including:

• In vitro / cell culture-based models
• Ex vivo studies using disease models or human-derived tissues
• In vivo investigations in small preclinical models (subject to time and resource availability)
• Computational analysis and machine learning approaches to identify novel biomarkers and pathways of interest

This is a highly multidisciplinary project, involving close collaboration and interaction with experts across diverse fields. The successful applicant will receive comprehensive training in all relevant areas, including but not limited to molecular biology, immunology, infection biology/microbiology, and integration of multi-omics technologies. A key emphasis of the project is on applying these tools to enable an in-depth investigation of disease mechanisms and to identify novel biomarkers with translational potential for future clinical applications.

The student will benefit from a vibrant, collaborative research environment with access to cutting-edge facilities. Opportunities for collaboration with clinical researchers, as well as national and international partners, will also be available.

General Admissions

You'll need a good first degree from an internationally recognised university (minimum upper second class or equivalent, depending on your chosen course) or a Master’s degree in biomedical sciences, immunology, microbiology OR a related area. In exceptional cases, we may consider equivalent professional experience and/or qualifications. English language proficiency at a minimum of IELTS band 6.5 with no component score below 6.0.

How to apply

We’d encourage you to contact Dr Murphy Wan (murphy.wan@port.ac.uk) to discuss your interest before you apply, quoting the project code: MPB10001025

When you are ready to apply, please follow the 'Apply now' link on the Pharmacy, Pharmacology and Biomedical Sciences PhD subject area page and select the link for the relevant intake. Make sure you submit a personal statement, proof of your degrees and grades, details of two referees, proof of your English language proficiency and an up-to-date CV.

Funding Notes

Funding availability: Self-funded PhD students only.

PhD full-time and part-time courses are eligible for the UK Government Doctoral Loan (UK and EU students only – eligibility criteria apply).

Some PhD projects may include additional fees – known as bench fees – for equipment and other consumables, and these will be added to your standard tuition fee. Speak to the supervisory team during your interview about any additional fees you may have to pay. Please note, bench fees are not eligible for discounts and are non-refundable.