Date of Completion

2023

Document Type

Honors College Thesis

Department

Biology

Thesis Type

College of Arts and Science Honors, Honors College

First Advisor

Alicia Ebert

Keywords

VARS, tRNA-synthetase, translation, retina, neurodevelopmental disorder, zebrafish

Abstract

Protein synthesis is a necessary process for the creation and maintenance of all living beings. Aminoacyl tRNA synthetases (AARS) are a critical class of proteins that facilitate this process. By attaching amino acids- the building blocks of all proteins- to their corresponding tRNA molecules, AARS proteins allow the tRNAs to transport amino acids to the ribosome, and add it to the growing polypeptide length. The AARS enzyme specific for the transport of the amino acid valine, called valine aminoacyl tRNA synthetases (VARS), is known to be disrupted by a missense mutation of the VARS gene. In people affected by this disorder, the mutation causes microencephaly, microphthalmia, global developmental delays, and a severely shortened lifespan.

While VARS is expressed in every cell in the human body, the VARS mutation phenotype is seen primarily in the nervous system. The microphthalmia that has been observed is poorly understood, so we propose to use a zebrafish model of the VARS mutation to explore whether the small eyes are due to increased cell death or decreased cell proliferation. We will also investigate whether the cell layers of the eye are affected evenly or not. Through this research, we found that VARS mutants displayed both increased cell proliferation and cell death at certain stages in development, and that cell layers within the retina were impacted evenly by this mutation.

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

Download

Available for download on Monday, May 05, 2025

Share

COinS