Oral–systemic links: periodontal microbes and the blood-brain barrier

About the Project

Oral health is increasingly recognised as an important influence on brain health, including in cognitive disorders. Large population studies have implicated periodontitis as a significant risk factor for cognitive decline and dementia. Although inflammation is often suggested as driving this link, far less attention has been given to the direct effects of periodontal microbes and their metabolites upon the brain, despite the intense study of the parallel gut microbiota-brain axis.

One key example is Porphyromonas gingivalis, a common periodontal pathogen that produces bioactive organosulfur molecules known to enter the blood. We have shown that these metabolites can potently damage blood-brain barrier (BBB) integrity in human model systems, a highly significant finding given that similar BBB dysfunction accumulates with age1 and represents a major risk factor for cognitive decline2.

This PhD project will build on this work to deepen our understanding of how oral bacteria influence the cerebral vasculature and ultimately cognitive function in humans. Our overall aims are to:

1) Identify the molecular pathways through which P. gingivalis-derived organosulfur metabolites affect the BBB

You will use our established microbial-endothelial co‑culture model to investigate how organosulfur compounds disrupt BBB structure and function in vitro. This will include using endothelial functional assays, RNAseq transcriptomics, immunohistochemistry, and targeted genetic/pharmacological inhibition studies3–5.

2) Combine human microbiome, metabolomic, and cognitive data to understand how oral health relates to BBB integrity and cognitive performance

Working with volunteers recruited from Royal London Dental Hospital (healthy, gingivitis, periodontitis), you will integrate information on clinical status, oral microbial composition, metabolite load, immune markers, and BBB‑related biomarkers with validated online cognitive testing.

3) Test the functional impact of human serum on BBB models to link clinical observations with mechanistic findings

Serum from volunteers of different oral health status will be applied to our in vitro BBB model to confirm the association between circulating organosulfur metabolites and endothelial function5,6.

Through this integrated, interdisciplinary approach, you will help define how oral microbial metabolites influence the BBB and brain, explaining links between oral health and cognitive decline. Your findings will highlight potential intervention points to support the development of strategies targeting the oral microbiota to promote life-long cognitive health.

This project is part of the Advancing Translation of Oral Health Research (https://atohr.org/) BBSRC-funded Industrial Doctoral Landscape Award in collaboration with Haleon. This unique collaboration of five leading UK universities provides students with opportunities to conduct cutting-edge oral health research while gaining valuable industry experience. The programme spans four years and includes comprehensive training in oral health research and transferable skills, preparing graduates for successful careers in academia, industry, or the public sector. Our vision is to promote an interconnected network between academia and industry through state-of-the-art interdisciplinary studentships where multi-partner co-operation will facilitate a broad range of expertise that will develop world-class PhD students. This will be catalysed by identifying core technical, analytical and interpersonal skills required by Haleon’s oral health strategy. Haleon is a global leader in consumer health, with a portfolio of world-leading brands trusted by millions of people around the globe.

Person Specification

Essential qualities

We are looking for a highly motivated candidate with:

• A strong academic background, ideally with a First‑class degree or MSc (or international equivalent) in a relevant discipline such as neuroscience or microbiology.
• Genuine enthusiasm for interdisciplinary work that links microbiology, vascular biology, neuroscience and clinical dentistry.
• A collaborative mindset and willingness to contribute to a dynamic research team.
• Evidence of research ability through coursework, research projects, or laboratory experience.

Desirable experience

While not required, experience in any of the following areas would strengthen your application:

• Wet‑lab techniques such as mammalian cell culture, molecular biology methods, or immunohistochemistry.
• Bioinformatics or computational analysis, particularly RNAseq or related ‘omics approaches.
• Prior experience in working alongside clinical teams or with human participant studies.

Funding

This 4-year studentship includes a tax-free stipend at London-weighted UKRI rates with an additional £3000 industry uplift per year

To classify for Home Fees, this typically means the candidate will have unrestricted access on how long they can remain in the UK (i.e. are a British National, have settled, or pre-settled status, have indefinite leave to remain etc.). This is due to funding restrictions.

How to apply:

Formal applications must be submitted through our online form by the stated deadline for consideration. Applicants are NOT required to submit a research proposal as part of the application.

Applicants are required to submit the following documents:

• Your CV
• A Personal Statement, including:
  • Previous experience relevant to the project
  • Your motivations for pursuing this position
  • Your career aspirations
  • Any further information you think is relevant to the application
• References
• Copies of academic transcripts and degree certificates

Informal enquiries about the project can be sent to Dr. Simon McArthur or Dr. Abish Stephen

Admissions-related queries can be sent to Dr. Aneesh Chandran

Information about the application process can be found (here)

Apply Online (here)

Please input Dr. Simon McArthur as primary supervisor when applying to this position.

Funding Notes

This is a 4 year fully funded project, and part of the BBSRC-Haleon Industrial Doctoral Landscape Award, open to students with UK Home fees eligibility.

To classify for Home Fees, this typically means the candidate will have unrestricted access on how long they can remain in the UK (i.e. are a British National, have settled, or pre-settled status, have indefinite leave to remain etc.).

This 4-year studentship includes a tax-free stipend at London-weighted UKRI rates with an additional £3000 industry uplift per year.