DREAMS · Describing the Role of the Epstein-Barr virus And S1PR inhibition in the pathogenesis of Multiple Sclerosis

Multiple Sclerosis (MS) is a demyelinating disease of the central nervous system (CNS). One million people in Europe have MS, experiencing a significantly reduced quality of life and dying 7-14 years younger than average. The annual burden on European economies is ~€35B. Epstein-Barr virus (EBV) infects almost all Europeans and is aetiologically linked to MS with infection increasing disease risk 32-fold. Despite the huge personal, societal and economic impacts of MS, the underlying role of EBV in its development remains poorly understood.DREAMS will explore how EBV contributes to MS development. To do this, the Postdoctoral Fellow (PF) will utilise a novel humanised mouse model which harbours the major genetic risk factor for MS and is permissive for EBV infection. This model displays characteristics common with human MS, including CNS immune cell infiltration. Applying multiplex immunofluorescence, the PF will explore the nature of this immune infiltrate and how it is influenced by drugs used to treat MS, focussing on inhibitors of S1PR signalling. Combined with mechanistic in vitro studies to determine how these drugs interact with EBV-infected B-cells and EBV-specific T-cells, this work will allow new insights into how S1PR modulation affects MS immunopathology. As such, this research aligns with the Horizon Europe Health cluster and several UN sustainable goals, and meets Open Science, Gender Equality, Supervision and Green Charter guidelines.The PF will receive training in humanised mouse models, in vivo imaging and flow cytometry during an outgoing 24-month phase at the University of Zurich (Switzerland). This will be followed by a 12-month return phase at the University of Limerick (Ireland), learning in vitro T-cell assays. The PF will leverage the interdisciplinary supervisory team to meet the research & training objectives outlined, in preparation for an independent research career in the field of virus-associated diseases.