Barbara Hull (Committee Member), Shulin Ju (Advisor), Labib Rouhana (Committee Member)
Master of Science (MS)
Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative motor neuron disease that causes progressive paralysis and death by asphyxiation. There is no cure or effective treatment; however, previous research has identified several genes that appear related to the pathology of ALS. When mutated, these genes result in proteins that gain toxic functions and disrupt normal cellular processes. Fused in Sarcoma (hFUS) is a human transcription factor in the nucleus that binds to DNA and RNA. Mutations in hFUS are associated with both familial and sporadic cases of ALS, frontotemporal lobar degeneration (FTLD), and cancer. In ALS and FTLD, hFUS is mislocalized to the cytosol where it interacts with stress granules and forms aggregates. This aggregation and cytotoxicity has been previously studied in budding yeast; however, study in fission yeast may provide unique information. Fission yeast has several genetic advantages over budding yeast for modeling mammalian cell biology, such as 43% of genes contain introns and they posess a similar alternative splicing mechanism. Mammalian and fission yeast cells also both contain microRNA as well as similar cell growth cycles. In this project, I established a fission yeast model of hFUS and showed that hFUS is toxic when overexpressed in fission yeast. Both localization to the nucleus and mislocalization to the cytosol occurred during overexpression of hFUS. In addition, fission yeast homologues to previously identified budding yeast toxicity suppression proteins were able to suppress hFUS toxicity, suggesting the suppression mechanism is conserved.
Department or Program
Department of Biological Sciences
Year Degree Awarded
Copyright 2016, all rights reserved. My ETD will be available under the "Fair Use" terms of copyright law.