2025-26 Project (Sadiq & Reljic)

The role of non-genital Chlamydia trachomatis infection in autoimmunity

SUPERVISORY TEAM

Supervisor

Professor Tariq Sadiq at City St George’s
Email: ssadiq@sgul.ac.uk

Co-Supervisor

Professor Rajko Reljic at City St George’s
Email: rreljic@sgul.ac.uk

PROJECT SUMMARY

Project Summary

This is a tremendous opportunity to work nationally in the field of sexually transmitted infections (STIs) whilst gaining and refining significant expertise in laboratory-based genome sequencing, bioinformatics and immunology. This PhD will work predominantly with national collaborators in the UK in a novel area of investigation of the relationship of non-viral STIs and autoimmunity, including on how STI pathogenesis is influenced by bacterial and immunological environments in the genital and gastrointestinal tract.

Project Key Words

STIs, auto-immunity, chlamydia trachomatis, microbiome

MRC LID Themes

Infectious Disease
Global Health

Skills

MRC Core Skills

Quantitative skills
Interdisciplinary skills

Skills we expect a student to develop/acquire whilst pursuing this project

The successful candidate will learn and customise laboratory techniques including 16SrRNA long-read sequencing, mucosal and systemic immune cell composition studies viability PCR, appropriate bioinformatic and statistical training.

Routes

Which route/s are available with this project?

1+4 = No
+4 = Yes

Possible Master’s programme options identified by supervisory team for 1+4 applicants:

Not applicable

Full-time/Part-time Study

Is this project available for full-time study? Yes
Is this project available for part-time study? Yes

Location & Travel

Students funded through MRC LID are expected to work on site at their primary institution, meeting – at the minimum – the institutional research degree regulations and expectations. Students may also be required to travel for conferences (up to 3 over the duration of the studentship), and for any required training (for research degree study). Other travel expectations and opportunities highlighted by the supervisory team are noted below.

Primary location for duration of this research degree: City St George’s, London

Travel requirements for this project: The candidate will make site visits to sexual health clinics predominantly in London.

Eligibility/Requirements

Particular prior educational requirements for a student undertaking this project

Minimum City St George’s institutional eligibility criteria for doctoral study.
Relevant MSc preferred, eg immunology of infection; Medical Microbiology; Applied Biomedical Science; Genomic medicine; Global Health, Infection and Immunity

Other useful information

Potential Industrial CASE (iCASE) conversion? = No

PROJECT IN MORE DETAIL

Scientific description of this research project

This PhD will explore how the sexually transmitted infection, Chlamydia trachomatis (CT) infection, may predispose to autoimmunity, particularly when infecting the anorectum of men and women. Genital CT and some gut infections, such Shigellosis, which is sexually transmissible among men who have sex with men (MSM), have been associated with sero-negative autoimmune reactive arthritis, which is frequently managed with antibiotics against CT. Such reactions occurring with gut infection may be linked to dissemination of chlamydia antigens. For CT, the importance of anorectal and oropharyngeal infection in this association is unclear as is whether non-genital CT plays a role in autoimmunity generally. This is important as anorectal CT is not only common among MSM but is now recognised to be more common than previously thought among women. Non-genital CT may also impact gut microbiota, leading to dysregulation of local and systemic immunity, a further potential factor in this relationship.

Project objectives
1. define immunological responses to CT infection diagnosed in the genital tract, anorectum and oropharynx, in both men and women, within sexual health clinics.
2. describe changes in immune response after CT treatment.
3. investigate associations of the mucosal microbiome with these responses.

2. Techniques to be used
Long-read 16S rRNA PacBio-HiFi sequencing for microbiome analysis; CT-viability PCR to discriminate infection from contamination in female samples. Immune cell composition in all mucosal sample types: staining for lymphocytes (CD4+, CD8+ T-cells, B cells), monocytes/macrophages, neutrophils, NK cells and unconventional T cell populations; immune cell antigen proliferation studies on peripheral blood; For CT infection, peripheral blood monocytes (PBMC) obtained from blood samples in confirmed viable CT infection and controls will be stimulated with Hsp60 antigen of CT and analysed for proliferation; high throughput auto-immune protein array screen will also be considered.

3. Confirmed availability of any required databases or specialist materials
We have confirmed access to mucosal and serum excess diagnostic samples from across south-west London (Dr Tim Planche, Consultant Microbiology, South West London Pathology [SWLP]); we have confirmed collaboration with our clinical partners at Croydon University Hospitals and if necessary Chelsea and Westminster Hospitals.

4. Potential risks to the project and plans for mitigation
A favourable ethics opinion will be sought and we do not consider the project to raise any significant ethical, legal or management issues. The processes employed for collecting samples will be routine and safe. We have several clinics agreeing to support the work, to act as contingency; the incidence of anorectal infections in the collaborating clinics are sufficiently high.

Timelines
Year1: Co-design and obtaining ethics approval for year 2 clinical recruitment. Systematic review on quantitative immunological responses to CT; familiarisation with laboratory techniques using SWLP samples. Submit upgrade report.
Year2: Patient recruitment; appropriate sample collection and storage for immunological work; familiarisation with several long-read 16S rRNA microbiome pipelines using R-based packages such as DADA2, Phyloseq and Vegan.
Year 3: Immunological work and analysis; Microbiome DNA library preparation; Sequencing will be done in-house or outsourced to Earlham Institute, with which the group has an ongoing collaboration. Microbiome analysis.
Year 4: Finalise analyses. Prepare write up and submit thesis.

Additional information from the supervisory team

The supervisory team has provided a recording for prospective applicants who are interested in their project. This recording should be watched before any discussions begin with the supervisory team.

Sadiq-Reljic recording

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