The genetics of MS severity - an investigation of the P2X7 Receptor

MS is a chronic neuroinflammatory condition with associated demyelination and neurodegeneration. The most common form of MS is relapsing-remitting (RRMS) where new symptoms occur in isolated attacks (relapses) which can lead to permanent neurological deficits. The outcomes of people with MS are highly variable, some accumulate a lot of disability, despite the use of effective immunotherapies, whilst others accumulate little disability. Our recent work characterising the genetic architecture of MS severity, has demonstrated that progressive MS is associated with an overrepresentation of genes expressed in CNS compartments. Specifically, we have identified signals involving synaptic plasticity, oligodendroglial biology and cellular senescence in being associated with more severe MS. Additionally, we have been investigating the role of innate immune cells, namely monocytes and microglia and their role in MS pathogenesis and outcomes. Specifically, we are interested in a purinergic receptor, P2X7 and its role in microglial activation, and MS outcomes. In this project, you will work with two lead researchers in the Department of Neuroscience, A.Prof Vilija Jokubaitis (neuroscientist), and A.Prof Mastura Monif (neurologist), collaborating on understanding whether or not genetic variation in the P2X7 receptor impacts MS severity outcomes. If you are interested in clinical neurology, genetics, bioinformatics and biostatistics, this project is for you. In this project, you will learn bioinformatic analysis skills to determine whether genetic variation in the P2X7 gene modulates disease outcomes, in a cohort of over 2,000 people with MS. You will also be co-supervised by Dr Jingni He, an expert in bioinformatics.