Infection-Driven Mechanisms of Inflammatory Arthritis

PROJECT OVERVIEW

Immune-mediated inflammatory arthropathies, including Juvenile Idiopathic Arthritis (JIA), Rheumatoid Arthritis (RA), Psoriatic Arthritis (PsA), and therapy-induced inflammatory arthritis, are chronic disabling conditions whose initiating triggers remain poorly understood. Increasing evidence suggests that bacterial and viral infections may initiate or perpetuate inflammatory responses within the joint, yet the molecular and cellular pathways linking infection to chronic synovial inflammation remain largely undefined.

This PhD project will investigate how viral and bacterial pathogens contribute to the development and persistence of inflammatory arthritis. Chikungunya virus (CHIK) provides an important model of infection-induced inflammatory arthritis, as many patients develop prolonged, painful polyarthritis following acute infection. Similarly, tick-borne and companion animal-associated pathogens, including Borrelia burgdorferi, Borrelia mayonii, Borrelia hermsii, and Bartonella henselae, are associated with chronic joint and lymph node inflammation. In addition, common latent viral infections such as cytomegalovirus (CMV) and Epstein–Barr virus (EBV) have been implicated in autoimmune disease, although their contribution to chronic inflammatory arthritis remains uncertain.

The successful candidate will combine clinical sample acquisition with cutting-edge multi-omics technologies to define the cellular and molecular mechanisms through which infection shapes the inflammatory synovial microenvironment. Using ultrasound-guided synovial biopsies and matched peripheral blood samples from patients, the project will integrate single-cell RNA sequencing, spatial transcriptomic and proteomic imaging, serum proteomics, and advanced computational systems biology to generate an unprecedented map of infection-associated immune responses within human joints.

A major focus will be to characterise adaptive immune responses through T-cell and B-cell receptor repertoire analysis, while defining transcriptional programmes within innate immune populations, including monocytes, macrophages, and neutrophils. These datasets will be integrated with analyses of stromal cells, including synovial fibroblasts and endothelial cells, to identify how microbial products, persistent viral transcripts, or bacterial components influence tissue-resident cells, immune cell crosstalk, and the establishment of chronic inflammation.

The project will seek to determine whether distinct microbial signatures or pathogen-associated molecular pathways are shared across different inflammatory arthropathies or define specific disease endotypes. By comparing infection-driven arthritis with established immune-mediated diseases, the research will identify common inflammatory pathways.

The long-term objective is to establish a mechanistic framework linking infection to chronic inflammatory arthritis that can inform improved prevention and treatment strategies. These findings could support the development of vaccination strategies for high-risk populations, identify patients who may benefit from targeted antimicrobial therapies alongside immune-modulating drugs, and provide new approaches to preventing or treating chronic joint pain and inflammation. More broadly, understanding infection-driven immune activation has the potential to transform our understanding of inflammatory arthritis arising from currently unknown triggers.

This is a highly translational clinical research project embedded within an interdisciplinary team of clinician-scientists, immunologists, and computational biologists. The successful applicant will receive comprehensive training in musculoskeletal ultrasound-guided synovial biopsy, human immunology, single-cell and spatial multi-omics technologies, and systems biology approaches to translational medicine.

Essential requirements: Applicants must hold full GMC registration with a licence to practise and be willing to undertake clinical research within the Experimental Medicine Clinical Research Facility, including performing ultrasound-guided synovial biopsies and working directly with patients.

KEYWORDS

Inflammation, arthritis, infection, scRNAseq, systems-immunology

TRAINING OPPORTUNITIES

The applicant will work with biopsy teams to obtain synovial biopsies. They will gain key experience in human tissue biology processing, spatial imaging and systems immunology including analysis of single cell biology and spatial transcriptomics.

KEY PUBLICATIONS

The applicant will work with biopsy teams to obtain synovial biopsies. They will gain key experience in human tissue biology processing, spatial imaging and systems immunology including analysis of single cell biology and spatial transcriptomics.

THEMES

Experimental Medicine, Inflammation & Immunology, interacting systems, systems biology

CONTACT INFORMATION OF ALL SUPERVISORS

Mark Coles

Christopher Buckley

Calliope Dendrou

Sarah Davidson