Introduction

Myalgic encephalomyelitis (ME) is a multifactorial disorder affecting the nervous system characterised by severe and prolonged fatigue. The cause is unknown although alterations in the immune system, recurrent or persistent infections, that can originate in the gut, autoantibody production and the effectiveness of B cell-depletion therapy suggest that ME patients suffer from autoimmune responses. This multidisciplinary project provides an opportunity for extensive training in virology, animal and cell biology, ‘omics', and bioinformatics.

The Team

The student will benefit from extensive knowledge and technical expertise of senior scientists in the groups of Profs Wileman and Carding at the UEA-Norwich Medical School. The project also benefits from collaborative work with Cornell University (USA), which is undertaking a parallel project with a USA cohort of ME patients.

Project Description

Myalgic encephalomyelitis (ME) is a multifactorial disorder affecting the nervous system characterised by severe and prolonged fatigue. The cause is unknown although alterations in the immune system, recurrent or persistent infections, that can originate in the gut, autoantibody production and the effectiveness of B cell-depletion therapy suggest that ME patients suffer from autoimmune responses.

Indeed, patients with ME have altered immune signatures indicative of viral infection with most patients having persistent or intermittent symptoms of gastrointestinal dysfunction, with a significant subset presenting with chronic enterovirus infection of the stomach.

In contrast to acquired environmental virus infections, there is evidence that alterations in virus populations resident in the human gut (the gut virobiota) are linked to the development of inflammatory diseases (3).

This PhD project will investigate whether the underlying causes of ME are related to the presence of specific virus populations within the gut virobiota. Using high throughput DNA/RNA sequencing technology and bioinformatics tools we will determine if and how both resident gut bacteria and virus populations changes with disease progression and if a distinct virobiota signature can be identified in ME patients.

Functional studies will establish whether the virobiota of ME patients contains viruses able to kill commensal bacteria (bacteriophages) and invade host cells in the gut (eukaryotic viruses), and can invoke local and systemic inflammatory immune responses.
The aim of this study is to examine the intestinal virome of ME patients in relation to microbiome alteration and disease pathogenesis. This will involve refinement of current viral extraction techniques and development of a bioinformatic pipeline for data analysis.

Funding

Funding is via Invest in ME Research and UEA.

References