Organization of Translation in Brain Astrocytes under Stress

Eukaryotic translation Initiation Factor 2B (eIF2B) is a master regulator of protein synthesis. The transient downregulation of its activity under stress conditions is important for survival. Partial loss-of-function mutations in any of the five genes encoding the subunits of eIF2B lead to a recessive cure-less neurodegenerative disease, termed Vanishing White Matter (VWM). Brain astrocytes are known to be central for the disease. In my work, I am applying computational methods on data obtained from astrocytes isolated from brains of eIF2B^5R132H/R132H mice and WT controls. The transcription data (RNA-seq) and translation data (Ribo-Seq) revealed important novel details about immune defense mechanisms mediated by transcriptional and translational programs under constant stress, caused by the reduced activity of mutant eIF2B in VWM disease.