An overview of projects and techniques used in the Axo-Glial Group

Function of the myelinic channel – the oligodendrocyte’s highway to the axon

“We are interested in the function of the myelinic channel, as a route by which the myelinating cell effects trophic support for the axon. This work follows on from a series of publications beginning with Griffiths, Nave and colleagues in 1998 and Edgar, Griffiths, Nave and colleagues 2004.” – Dr Katie Chapple, Postdoc.

This work is conducted in collaboration with the Nave Lab at the Max Planck Institute of Experimental Medicine, Goettingen, Germany.

Schematic provided by Gemma Thomson.

Tropism and pathogenesis of Zika virus in the central nervous system

“We are interested in the tropism and pathogenesis of Zika virus infection in the nervous system in the developmental period immediately following neurogenesis. Our in vitro and in vivo data demonstrate that oligodendrocytes and astrocytes are particularly susceptible to infection, whilst oligodendrocytes and their myelin sheaths are most vulnerable to injury.

This work is conducted in collaboration with the Neurozika group at the University of Glasgow, including Hugh Willison, Alain Kohl, Christopher Linington and Sue Barnett.

The role of Fibroblast growth factors in MS

“Increasing evidence suggests neuronal pathology causing chronic disability in multiple sclerosis (MS) might occur independently to demyelination. My work focuses on fibroblast growth factor 9 (FGF9), which is up-regulated in MS lesions and also in the hippocampus of patients with major depressive disorders (MDD) as a major facilitator of neuronal pathology. We use in vitro tools to study the role of FGF9 on neuronal cell death, which ultimately leads to axonal loss, secondary demyelination and accumulation of activated microglia/macrophages. The main techniques are primary glial and neuronal cell culture, immunofluorescence imaging, and in-house developed automated image analysis tools.” – Dr Katja Th├╝mmler, Postdoc.

Metabolic characteristics of oligodendrocytes

“Oligodendrocytes are the myelin forming cells of the central nervous system. They ensheath axons to provide insulation and crucial metabolic support. We know from the literature that post-myelination oligodendrocytes are glycolytic cells that, in principle, can survive by glycolysis alone. As glycolysis per se does not require oxygen, post-myelination oligodendrocytes should, in principle, not require oxygen for energy production. However, in models of hypoxic neuroinflammation the myelinating oligodendrocyte is particularly susceptible. We carry out experiments to understand oligodendrocyte metabolism using tools such as primary CNS cell culture, cell-type enriched cultures, live imaging, immunocytochemistry, real-time quantitative PCR, and lipid analysis.” – Colin Crawford, PhD Student

Funded by SPRINT-MND/MS, 3-year PhD studentship, 2017-2020.

The pathophysiological significance of intra-thecal antibody responses to lipids in multiple sclerosis

“Lipid-specific IgM antibodies found in multiple sclerosis (MS) patients have been associated with a reduced risk of developing progressive multifocal leukoencephalopathy, a fatal side-effect of some MS therapies caused by infection of the central nervous system (CNS) by John Cunningham virus. Preliminary transcriptomic data indicated that these antibodies were triggering an antiviral immune response in the CNS. The aim of this project is to investigate the antiviral properties of these antibodies and to unravel their mechanism of action. This will be achieved using antibody purification, cell culture, real-time quantitative PCR, immunocytochemistry, fluorescent in situ hybridisation, virus infection and plaque assays.” – Lorna Hayden, PhD Student.

Funded by Medical Research Scotland, 4-year PhD studentship, 2017-2021.