Research Projects

This project aims to investigate the potential involvement of Irgm1 (Immunity-related GTPase family M member 1) in regulating the inflammatory response of microglia, the resident innate immune cells of the central nervous system (CNS). Growing evidences have identified chronic neuroinflammation mediated by microglia plays a pivotal role in the onset and progression of several neurological diseases, including but not limited to Neurodegenerative diseases, Sepsis Associated Encephalopathy (SAE) and in Age associated neurodegeneration. The findings reveal that in all these diseases microglia exhibit a chronically activated proinflammatory phenotype which is associated with impaired homeostatic functions like phagocytosis, autophagic degradation of toxic proteins and amyloid plaques, as well as tissue repair properties. However, much remains unknown about the molecular underpinnings that govern microglial activation, phenotypic transformations, phagocytosis and clearance of toxic proteins. This knowledge is vital for developing therapeutic interventions that may modulate microglial immune response towards a protective phenotype preventing chronic neuroinflammation. Irgm1, an immunity-related GTPase, is known to regulate immune responses in peripheral immune cells primarily through autophagy, which makes it a significant protein of interest. However, its role in the CNS immune landscape is poorly explored. Specifically, its involvement in regulating microglial function, polarization or its impact on neuroinflammation have not been studied. This project will characterize the expression and function of Irgm1 in microglia under both normal and inflammatory conditions. Using genetic models of Irgm1 knockout cells, we will assess the effect of Irgm1 on microglial activation and polarization, phagocytosis and chemotaxis, cytokine production, autophagic degradation of amyloid fibrils and neuroinflammatory pathways. In addition, the study will examine the various cellular and molecular pathways affected by Irgm1 in microglia by high throughput RNA sequencing method. Overall, this project would unravel a novel regulatory pathway in microglial activation, polarization and neuroinflammatory signalling. It will also significantly enhance our understanding into the complex molecular pathways that govern microglial immune response which will have therapeutic implications. Findings from this study will bear significance and relevance in a range of neurological disorders, particularly, Alzheimer’s disease, SAE and age-related neuroinflammation.