Principal Supervisor: Dr Jennifer HeaneyLink opens in a new window

Co-supervisor: Professor Iain Chapple; Dr Nabil Quraishi; Professor Tariq Iqbal

PhD project title: Immunobiology of oral, intestinal & systemic health

University of Registration: University of Birmingham

Project outline:

Background and objectives

Microbiome imbalance can cause immune dysregulation that can drive a range of non-communicable, inflammatory-based diseases. Similarly, altered host immunity can impact upon the microbial environment and shift the balance from symbiosis to dysbiosis. The mouth and gut host the most complex microbiomes of the human body. Bi-directional relationships between oral and gastrointestinal systems can influence the onset and progression of inflammatory-based disease. Oral inflammation and associated microbiome dysbiosis impact the gut microbiome, inducing immune-inflammatory changes, and vice versa. Bacterially induced oral inflammation (periodontitis) not only influences the gut but the subsequent immune response affects tissues and organs throughout the body. Oral bacteria leak into the blood circulation and directly contribute to systemic disease. Equally, poorly controlled systemic inflammatory diseases can feedback into oral and gut immune-inflammatory responses.

Whilst advances have been made in understanding connections between oral, intestinal, and systemic health, these relationships remain unclear and complex. The objective of this project is to enhance understanding of the immunobiology of the oral-gut-systemic axis to advance insights into crosstalk between systems in health and disease. Ultimately, this knowledge could influence future screening, diagnosis and management of patients with diseases driven by immune-inflammatory-microbiome dysregulation.

Methods

The project is a collaboration between the Clinical Immunology Service, The School of Dentistry and The Microbiome Treatment Centre teams based at the University of Birmingham. The project will bolt onto existing infrastructure and ongoing/future studies.

Investigations will take place in clinical populations (pre- and post-treatment) and healthy donors to understand oral-gut-systemic interactions in health and disease. The project will have access to a range of samples (blood, saliva, stool) from patients primarily with oral and gastrointestinal diseases (including inflammatory bowel diseases). Samples will be available from an ongoing inception cohort of patients before clinical intervention, and post-treatment (including patients who respond/do not respond to therapy).

A range of immunological analysis will be undertaken, using various techniques. Parameters of interest include investigations into humoral immunity (including intact immunoglobulins and free light chains), a range of inflammatory markers and cell populations that to date have been under-researched (such as neutrophils, B-cells) yet may piece together key information on bi-directional relationships across systems. To support investigations into mucosal immune responses/dysregulation, immunoglobulin-microbial complexes across systems will also explored.

Information and data already collected from the clinical studies underpinning this project will be available to support analysis, including clinical and biological phenotyping, microbial diversity, RNA-seq.

 

BBSRC Strategic Research Priority: Understanding the rules of life - Immunology

Techniques that will be undertaken during the project:

Quantitative ELISAs

Functional immune cell assays

Multiplex assays (O-Link)

Flow cytometry

IgA−SEQ

 

Contact: Dr Jennifer HeaneyLink opens in a new window