Theses and dissertations

This collection includes both ASU Theses and Dissertations, submitted by graduate students, and the Barrett, Honors College theses submitted by undergraduate students. 

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Development of a Novel Zebrafish Model for Dynamin-1 Epileptic Encephalopathy

Description
Epileptic encephalopathies (EE) are genetic or environmentally-caused conditions that cause “catastrophic” damage or degradation to the sensory, cognitive, and behavioral centers of the brain. Whole-exome sequencing identified de novo heterozygous missense mutations within the DNM1 gene of five pediatric patients with epileptic encephalopathies. DNM1 encodes for the dynamin-1 protein which…

Epileptic encephalopathies (EE) are genetic or environmentally-caused conditions that cause “catastrophic” damage or degradation to the sensory, cognitive, and behavioral centers of the brain. Whole-exome sequencing identified de novo heterozygous missense mutations within the DNM1 gene of five pediatric patients with epileptic encephalopathies. DNM1 encodes for the dynamin-1 protein which is involved in endocytosis and synaptic recycling, and it is a member of dynamin GTPase. The zebrafish, an alternative model system for drug discovery, was utilized to develop a novel model for dynamin-1 epileptic encephalopathy through a small molecule inhibitor. The model system mimicked human epilepsy caused by DNM1 mutations and identified potential biochemical pathways involved in the production of this phenotype. The use of microinjections of mutated DNM1 verified phenotypes and was utilized to determine safe and effective antiepileptic drugs (AEDs) for treatment of this specific EE. This zebrafish dynamin-1 epileptic encephalopathy model has potential uses for drug discovery and investigation of this rare childhood disorder.
ContributorsMills, Gabrielle Corley (Author) / Kodibagkar, Vikram (Thesis director) / Rangasamy, Sampath (Committee member) / School of Human Evolution & Social Change (Contributor) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05

Zebrafish models of Okur-Chung Neurodevelopmental Syndrome: Exploring Genotype-Phenotype Relationships

Description

Okur-Chung Neurodevelopmental syndrome (OCNDS) is a rare disorder characterized by hypotonia, developmental delay, dysmorphic features, and more. It is caused by pathogenic variants on CSNK2A1, the α subunit of protein kinase CK2. CK2 is considered a master regulator involved in many cell functions from cell differentiation and proliferation to apoptosis.…

Okur-Chung Neurodevelopmental syndrome (OCNDS) is a rare disorder characterized by hypotonia, developmental delay, dysmorphic features, and more. It is caused by pathogenic variants on CSNK2A1, the α subunit of protein kinase CK2. CK2 is considered a master regulator involved in many cell functions from cell differentiation and proliferation to apoptosis. Here, we create a potential zebrafish model of OCNDS with CK2 inhibition and characterize fibroblast cells with, K198R, D156E, and R47G variants of CSNK2A1. RNAseq results display a wide range of effects notably in the Myosin Protein superfamily, Insulin-like Growth Factor family, and in proteins related to mitochondrial function and cell metabolism. Factors in cell growth and metabolism across the nervous system and neuromuscular interactions appear to be most affected with similarities in markers to oncogenic states in some cases.
ContributorsLeka, Kamawela (Author) / Newbern, Jason (Thesis director) / Rangasamy, Sampath (Committee member) / Barrett, The Honors College (Contributor) / School of Molecular Sciences (Contributor) / Harrington Bioengineering Program (Contributor)
Created2023-05