JG Graves Fellowships Awarded by the Medical School
Congratulations to Dr Ryan MacDonald and Dr Roger Thompson who have each been awarded a JG Graves Medical Research Fellowship by the Medical School to support their research in the Department of Infection, Immunity & Cardiovascular Disease.
Dr Ryan MacDonald’s fellowship is entitled “Glial-Glial Interactions in Development and Disease”. Glial cells are a major component of the nervous system and are crucial for neuron survival and function. Despite their clear importance to neural function they remain highly understudied if compared to neurons.
The functioning of the vertebrate nervous system requires the co-ordinated activity of neurons which transmit electrical signals, microglia which provide immune functions and glia which provide physical support and regulate synapses and, with microglia, remove cellular debris. The shape and pattern of glial cells is critical to their function, and alterations in glial cell morphology are associated with nearly all neurological disorders (e.g. Motor Neurone Disease, Multiple Sclerosis and Alzheimer’s), either as cause or consequence. This is often manifested as gliosis, characterised by glial cells and microglia with changed shape, altered proliferative status and detrimental function. Neither the molecular pathways that govern glial cell patterning in development, nor the pathways involved in gliosis are known. Ryan will use the zebrafish retina as a model combined with RNA-seq, transgenesis, CRISPR mutagenesis and real time in vivo imaging to identify novel genetic mechanisms involved in gliosis and glial interactions. As the long-term clinical outcome is highly dependent on the degree of gliosis, understanding the molecular mechanisms behind each aspect of this process is critical for the repair and regeneration of the CNS.
Dr Roger Thompson’s fellowship is entitled ”Determining the mechanisms by which TLR3 signaling protects from development of PAH”
Pulmonary arterial hypertension (PAH) is a devastating condition characterised by progressive remodelling of pulmonary blood vessels leading to right heart failure and death. Roger has had a longstanding interest in PAH stemming from work undertaken at medical school on the effects of hypoxia on the pulmonary circulation at altitude and stimulated during his clinical training in the Sheffield pulmonary vascular diseases unit with Professor David Kiely.
In PAH, the mechanisms regulating vessel remodelling are poorly understood and treatments targeted at halting or reversing this process are lacking. The pattern recognition receptor, Toll-like receptor 3 (TLR3) is involved in the recognition of viral pathogens and emerging evidence suggests it also has a role in the regulation of vascular remodelling. Novel unpublished data implicate double-stranded RNA (dsRNA), a TLR3 ligand, in the pathogenesis of PAH. Through this JG Graves Fellowship, Roger plans to dissect the mechanisms by which dsRNA and TLR3 regulate vascular remodelling in PAH and to apply for further external fellowship funding. It is hoped this work will uncover new treatments that dampen or reverse PAH, which would make a huge difference to patients with this currently incurable disease