Fugger Group: Exploring the influence of Epstein-Barr virus (EBV) and glandular fever/infectious mononucleosis on the risk of multiple sclerosis (MS)

Lars Fugger

About the Research

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease affecting approximately 2.8 million people worldwide and is mostly affecting young women. The complex nature of MS is evident from the current therapeutic reliance on broad immune suppression, which does not prevent progressive damage through neurodegeneration Accordingly, there is an urgent need for more effective interventions based on precise target identification. We seek to understand the molecular basis of genetic factors and environmental interactions contributing to MS, strongly emphasising translational medicine.

Students joining our lab will be able to engage in a broad spectrum of research activities related to MS within a diverse interdisciplinary team, including clinicians and non-clinicians.

The cause of MS remains elusive, yet compelling evidence suggests that a complex interplay of genetic and environmental factors triggers the immune system to attack the central nervous system. Approximately 200 genetic risk variants, of which most lie in immune genes, collectively contribute to one-third of the total MS risk. Among non-genetic factors such as infections, vitamin level, obesity and smoking, EBV stands out as a major contributor to MS, increasing the risk of future MS by 32-fold. EBV is the most common and persistent virus infection in humans, affecting 90-95% of the world's population. EBV infection typically occurs within the first two decades of life and often runs asymptomatically in infants and toddlers, whereas it causes glandular fever in 20-70% of EBV-infected adolescents. Strong clinical and molecular evidence links elevated titres of EBV-specific antibodies and a history of glandular fever/infectious mononucleosis to MS.

We hypothesise that EBV infection, particularly when it manifests as glandular fever/ infectious mononucleosis, causes lasting changes in the immune system. We consider the age-specific manifestations of EBV infection, including glandular fever/infectious mononucleosis in teenagers, as key to identifying and understanding these processes that may increase the risk of MS later in life.

Accordingly, we aim to analyse tonsil biopsies and blood samples using flow cytometry, transcriptomic and proteomic techniques to elucidate the molecular mechanisms underpinning EBV and the rarer CMV and HHV6 infections, and their potential roles in the development of MS. By profiling cellular markers, proteins, and gene expressions, we aim to identify cells, biomarkers and pathways involved in the immune responses to these viruses.

Ultimately, this research will contribute to a better understanding of how these infections may influence the risk of developing MS, potentially leading to the development of preventative and therapeutic strategies to stop MS in its tracks. 

Training Opportunities

Students joining our lab will receive comprehensive training in:

Cellular Immunology Analyses: Students receive hands-on training in cellular immunology, focusing on the analysis of immune cell function, interaction, and behaviour. This includes techniques such as flow cytometry, T and B cell assays, and ELISA, allowing students to explore immune responses at the cellular level.

Single-Cell Technologies: Our lab is at the forefront of single-cell analysis, offering training in techniques such as single-cell RNA sequencing (scRNA-seq) and single-cell ATAC-seq. Students will gain experience in isolating, processing, and analysing individual cells to uncover heterogeneity within complex tissues.

Spatial Transcriptomics: Students can be trained in spatial transcriptomics, a technique that combines gene expression profiling with spatial information to map transcriptomic data within tissue samples. This training includes preparation of tissue sections, sequencing protocols, and data interpretation to understand spatial gene expression patterns.

Computational Biology: Our lab emphasizes the integration of computational approaches with experimental data. Training includes bioinformatics skills such as data analysis, statistical modelling, and the use of computational tools to interpret large-scale biological data, including genomic, transcriptomic, and proteomic datasets.

Students will be enrolled on the MRC Weatherall Institute of Molecular Medicine DPhil Course, which takes place in the autumn of their first year. Running over several days, this course helps students to develop basic research and presentation skills, as well as introducing them to a wide range of scientific techniques and principles, ensuring that students have the opportunity to build a broad-based understanding of differing research methodologies.

Generic skills training is offered through the Medical Sciences Division's Skills Training Programme. This programme offers a comprehensive range of courses covering many important areas of researcher development: knowledge and intellectual abilities, personal effectiveness, research governance and organisation, and engagement, influence, and impact. Students are actively encouraged to take advantage of the training opportunities available to them.

As well as the specific training detailed above, students will have access to a wide range of seminars and training opportunities through the many research institutes and centres based in Oxford.

The Department has a successful mentoring scheme, open to graduate students, which provides an additional possible channel for personal and professional development outside the regular supervisory framework. We hold an Athena SWAN Silver Award in recognition of our efforts to build a happy and rewarding environment where all staff and students are supported to achieve their full potential.

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Publications