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

主要目的是确定星形胶质细胞和小胶质细胞的稳态功能如何在自然衰老和病理过程中发生变化，以及胶质细胞表型变化的后果如何随后传递到神经元群体以诱导功能障碍和神经退行性变。一旦通信机制被描绘出来，就有可能确定“信息”的性质在自然衰老过程中以及在与Tau蛋白聚集相关的病理过程中是如何改变的。这种方法可以提供深入了解与衰老和病理学相关的功能障碍的分子过程，并可能突出新的干预机会。下一代分子技术将用于实现这些目标，包括：基于质谱的蛋白质组学; erce ellRNAseq;单分子阵列（SiMOA）;以及其他更传统的生物化学技术。

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.