SIGNATURE WORK
CONFERENCE & EXHIBITION 2023

Autosomal dominant Hereditary spastic paraplegia (AD-HSP) patients show weak locomotor activity. This condition is frequently caused by the loss of Spastin, a microtubule-severing enzyme. When loss of spastin is modeled in Drosophila, adults demonstrate weak locomotor activity while larvae show a unique bunched synaptic bouton morphology at the neuromuscular junction and weaker synaptic signaling. To further elucidate the mechanism of this pathway, Ozdowski et al. carried out a forward genetic screen and identified the loss of p21-activating kinase 3 (Pak3) as a suppressor of the spastin null phenotype. Pak3 has been shown to regulate actin filament dynamics by inhibiting the Rac pathway. Previous experiments showed that loss of Pak3 specifically in gliotactin-expressing cells suppresses the spastin null morphology, implicating Pak3 activity in the subperineurial glia as the cells responsible for the spastin mutant pathology. To confirm the role of this cell type, reduced Pak3 expression in cells expressing Moody, another protein widely found in subperineurial glia. Through immunostaining and confocal imaging, my result shows that the knockdown of Pak3 under the control of the moody promoter has a similar effect as with the gliotactin promoter. Given this promising result, I am interested in understanding the interaction of subperineural glia and neurons spatially and temporally through live-cell imaging. My preliminary imaging result shows that microfluidics is the best method to visualize the neurons and glia in vivo.

My three thematic courses (Cellular and molecular neurobiology, Behavioral neuroimmunology, Functional Neuroanatomy) and my capstone courses have been pivotal to the success of my signature work. Moreover, my experiential learning experiences e.g. tutoring, working in Sherwood lab and podcasting with MediHealth Podcast have cultivated my technical and soft skills and led to the culmination of my signature work.