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Fission Yeast as a Model Organism for FUS-Dependent Cytotoxicity in Amyotrophic Lateral Sclerosis

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2016, Master of Science (MS), Wright State University, Biological Sciences.
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.
Shulin Ju, Ph.D. (Advisor)
Labib Rouhana, Ph.D. (Committee Member)
Barbara Hull, Ph.D. (Committee Member)
70 p.

Recommended Citations

Citations

  • Cone, A. J. (2016). Fission Yeast as a Model Organism for FUS-Dependent Cytotoxicity in Amyotrophic Lateral Sclerosis [Master's thesis, Wright State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=wright1470750088

    APA Style (7th edition)

  • Cone, Alan. Fission Yeast as a Model Organism for FUS-Dependent Cytotoxicity in Amyotrophic Lateral Sclerosis. 2016. Wright State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=wright1470750088.

    MLA Style (8th edition)

  • Cone, Alan. "Fission Yeast as a Model Organism for FUS-Dependent Cytotoxicity in Amyotrophic Lateral Sclerosis." Master's thesis, Wright State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=wright1470750088

    Chicago Manual of Style (17th edition)