Using the Zebrafish Visuomotor Response Assay to Characterize the Behavioral Effects of FERRY Complex Mutations

Presenter

Colin McCaffrey Wood

Campus

UMass Amherst

Sponsor

Gerald Downes, Department of Biology, UMass Amherst

Schedule

Session 5, 3:30 PM - 4:15 PM [Schedule by Time][Poster Grid for Time/Location]

Location

Poster Board A65, Campus Center Auditorium, Row 4 (A61-A80) [Poster Location Map]

Abstract

The recently discovered Five-subunit Endosomal Rab5 and RNA/Ribose intermediarY (FERRY) complex is composed of 5 distinct proteins (TBCK, C12ORF4, PPP1R21, GATD1 and CRYZL1). As a whole, the complex is proposed to bind endosomes and shuttle mRNA to the periphery of the cell. Of the genes that encode these proteins, mutations in TBCK, PPP1R21, and C12ORF4 are known to cause severe neurodevelopmental disorders in humans. Notably, there are no known cures for any of these diseases and little is known about how mutation of each gene causes disease. We are using CRISPR-Cas9 gene editing technology to disrupt tbck, ppp1r21, and c12orf4 in larval zebrafish and subsequently analyzing their swimming behavior using a visuomotor response (VMR) assay. The visuomotor response is a well-characterized zebrafish behavioral response that causes zebrafish to startle when there is a sudden change in lighting conditions whether that be dark to light, or light to dark. I designed an Arduino-controlled light box in order to conduct this assay and control it with high temporal resolution. From this data, we aim to identify a behavioral phenotype that could allude to the neural circuits disrupted following mutation of these three genes. Once a phenotype has been established, it could be possible to attenuate the mutant zebrafish phenotype with small molecule drugs, which could hold therapeutic potential for patients. 

Keywords

Neurogenetics, Neurodevelopment , Disease modeling, Gene editing, Zebrafish

Research Area

Neuroscience and Cognitive Science

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