Ryan Mulligan, an MSTP (Grad3) student in the Winckler Lab, has been awarded an NIH F30 Fellowship studying lysosomal membrane permeabilization (LMP) in the nervous system. LMP is characterized by disruption of the lysosomal limiting membrane and leakage of luminal lysosomal contents into the cytosol, which is a common underlying feature across neuropathologic and aging brains. The fellowship will investigate the role of Rab7, an endosomal small GTPase, in directing immediate endosomal responses to neuronal LMP insults. Rab7 is a master regulator of late endosomal and lysosomal function, and genetic mutations in Rab7 cause the progressive peripheral neuropathy Charcot-Marie Tooth 2B (CMT2B). Ryan will explore the requirement of Rab7 activity on known LMP responses, such as induction of lysosomal specific autophagy, and how this may be impacted in CMT2B mutants. He will further investigate the impact of aging on the ability of wild-type and CMT2B mutant brains to degrade lysosomal bound cargos and respond to LMP. Overall, these studies will better elucidate cellular responses to disruptions in neuronal lysosomal function which could inform potential novel therapeutic approaches for a vast number of neurological disorders and the aging population.