Barrett

Barrett, The Honors College at Arizona State University proudly showcases the work of undergraduate honors students by sharing this collection exclusively with the ASU community.

Barrett accepts high performing, academically engaged undergraduate students and works with them in collaboration with all of the other academic units at Arizona State University. All Barrett students complete a thesis or creative project which is an opportunity to explore an intellectual interest and produce an original piece of scholarly research. The thesis or creative project is supervised and defended in front of a faculty committee. Students are able to engage with professors who are nationally recognized in their fields and committed to working with honors students. Completing a Barrett thesis or creative project is an opportunity for undergraduate honors students to contribute to the ASU academic community in a meaningful way.

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Characterization of mTOR Pathway and Reduced Neuronal Size Phenotype in Rett Syndrome Model

Description
Rett syndrome is a genetically based, X-linked neurodevelopmental disorder that affects 1 in 10,000 live female births. Approximately 95-97% of Rett syndrome cases are attributed to a mutation in the MECP2 gene. In the laboratory setting, key neuropathological phenotypes of Rett syndrome include small neuronal soma and nuclear size, increased…

Rett syndrome is a genetically based, X-linked neurodevelopmental disorder that affects 1 in 10,000 live female births. Approximately 95-97% of Rett syndrome cases are attributed to a mutation in the MECP2 gene. In the laboratory setting, key neuropathological phenotypes of Rett syndrome include small neuronal soma and nuclear size, increased cell packing density, and abnormal dendritic branching. Our lab previously created and characterized the A140V mouse model of atypical Rett syndrome in which the males are viable. Hippocampal and cerebellar granule neurons in A140V male mice have reduced soma and nuclear size compared to wild type. We also found that components of the mTOR pathway including rictor, 4E-BP-1, and mTOR, were reduced in A140V mutant mice. Quantitative PCR analysis also showed reduced IGFPB2 expression in A140V mice along with an upward trend in AKT levels that did not meet statistical significance. The objective of this study is i) to characterize the down regulation of AKT-mTOR pathway, and ii) to examine the effect of a genetic strategy to rescue mTOR pathway deficiencies in Mecp2 mutant mouse model. Genetic rescue of the mTOR pathway downregulation was done by crossing heterozygous female A140V mice with heterozygous male Tsc2 mice. Quantitative PCR analysis of A140V_Tsc2 RNA expression supported genetic rescue of mTOR pathway components, however, more testing is needed to fully characterize the rescue effect. Western blot analysis also showed reduction in phosphorylated AKT in Mecp2 A140V and T158A mutant mice, however, more testing is still needed to characterize the mTOR pathway in A140V_Tsc2 mice. Finally, other methods, such as a pharmacological approach, or transfection to increase mTOR pathway activity in cell lines, will be tested to determine if rescue of mTOR pathway activity ameliorate the Rett syndrome phenotype.
ContributorsGerald, Brittany Madison (Author) / Newbern, Jason (Thesis director) / Narayanan, Vinodh (Committee member) / Rangasamy, Sampath (Committee member) / School of Life Sciences (Contributor) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12

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