Investigation into the mechanisms of glial dysfunction during ageing and pathology, and subsequent adverse influences exerted on neurones

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The primary objective is to determine how the homeostatic functions of astrocytes and microglia change during natural ageing and during pathology, and how theconsequences of this change in glial phenotype are subsequently conveyed to the neuronal population to induce dysfunction and neurodegeneration. Once the mechanism(s) of communication have been delineated, it will be possibleto determine how the nature of the 'message' is altered both during natural ageing, and during pathology associated with Tau protein aggregation. This approach may provide insight into the molecular processes underlying the dysfunctionassociated with ageing and pathology, and potentially highlight novel opportunities for intervention. Next generation molecular techniques will be employed to fulfil these objectives, including: mass-spectrometry-based proteomics; singlecellRNAseq; Single Molecule Array (SiMOA); as wellas other more conventional biochemistry techniques.