What role do antibodies play in multiple sclerosis?

Medical Research Scotland
PhD Studentship Award

This project is one of 11 four year PhD Studentships funded by Medical Research Scotland (http://www.medicalresearchscotland.org.uk) to be delivered jointly by the named University and Company. The Studentship will provide the first-class academic and commercial training needed to equip the successful candidate for a science career in an increasingly competitive market.

"From diagnosis to function: the pathophysiological significance of intra-thecal antibody responses to lipids in multiple sclerosis." to be delivered by the University of Glasgow [Supervisors: Dr Julia Edgar and Professor Christopher Linington (both Institute of Infection, Immunity and Inflammation)] and EUROIMMUN UK Limited (https://www.euroimmun.com/startseite.html) [Company supervisor: Dr Christian Probst].

This project aims to investigate the pathophysiological significance of intra-thecal synthesis of lipid-specific antibodies in multiple sclerosis (MS). Accumulation of disability in progressive multiple sclerosis (PMS) has been attributed to axonal injury and loss caused by inflammatory mechanisms occurring behind an intact blood brain barrier. The most obvious manifestation of this sequestered response is the presence of oligoclonal bands (OCB) of immunoglobulin (Ig) in cerebrospinal fluid (CSF). This intrathecal antibody response is present in >90% of patients at diagnosis, but despite associations with a more aggressive disease course, its pathophysiological significance remains obscure. The specificity profile (antigen targets) of this intrathecal antibody response is complex and differs between patients; nonetheless, in many patients a significant proportion of these antibodies recognise myelin lipids. Our most recent studies suggest these lipid-specific antibodies contribute to disease development by inducing a complex interferon-α/β receptor-dependent increase in expression of pro-inflammatory chemokines and proliferation of microglia; a combination of effects that provide a logical explanation for reports intrathecal synthesis of lipid-specific antibodies is associated with increased inflammatory activity in the CNS of patients. We believe this effect might be responsible for maintaining an inflammatory milieu in PMS despite the blood-brain barrier being intact. In this project will use neural cell cultures, small animal surgical techniques, immunocytochemistry and molecular methods to validate this hypothesis and develop effective strategies to identify and treat patients at risk.

ENQUIRIES:

Enquiries should be sent by email to Dr Julia Edgar:
[Email Address Removed]

APPLICATIONS:

Candidates must have obtained, or expect to obtain, a first or 2.1 UK BSc Honours degree, or equivalent for degrees obtained outside the UK, in relevant discipline.

Applicants should send a CV, the contact details of 2 academic references (including email addresses) and a covering letter, explaining why the applicant wishes to carry out this project, by email to Dr Julia Edgar:
[Email Address Removed]

Interviews are expected to take place approximately 4 weeks after the closing date for applications.

It is anticipated that the PhD Studentship will start in September 2017.