Contributor
Anusha Iyengar, Jane Liu
Subject Area
Biological Sciences, General, Genetics, Molecular Biology, Neuroscience
Abstract
Spinal muscular atrophy (SMA) is an autosomal recessive disease that results from mutations in the Survival Motor Neuron (SMN-1) gene. Although SMN is a ubiquitously expressed protein that acts as an RNA-binding protein (RBP), SMA is characterized by the selective degeneration of motor neurons of the lower spinal cord. Despite a clear understanding of the genetic causes underlying SMA, the mechanisms associated with low SMN levels to disease pathogenesis remains unclear. Here, we investigate the role SMN-1 has in different tissues to begin understanding possible mechanisms. This project has three aims that has guided our experiments. The first aim is to discover which cells or tissues are responsible for the SMA phenotypes in C. elegans. Behavioral assays such as pumping, thrashing, and defecation are used as a measurement of health since defects in these areas are typical SMA phenotypes. Chapter 1 outlines the surprising discovery that the loss of smn-1 in neurons and muscles, as previously studied, did not result in any strong phenotypes, but rather the loss of smn-1 in the intestine cause defects similar to that of null smn-1 mutants. These findings represent a new area of study for a better understanding of SMA. More research is needed to begin to understand the connection between the intestine and the neuromuscular defects. The second aim looks at how deleting smn-1 in specific tissues alter patterns of gene expression. The results from Chapter 1 prompted us to survey the impact of the intestinal deletion of smn-1 on gene expression. In Chapter 2, RNA-sequencing data revealed a set of proteins produced in the intestine to be highly upregulated in smn-1 mutants. These proteins were found to be involved in the intracellular pathogen response (IPR) that provides resistance against proteotoxic stress. In relation to this type of gene expression profile, thermotolerant properties are exhibited with the mutants. The third aim studies possible mechanisms in the intestine that lead to the observed phenotypes. A unique observation was made while testing the health of smn-1 mutants. We observed in the lifespan assay that the intestinal KO of smn-1 was surviving longer on FUDR than on normal plates. Therefore, Chapter 3 examines the impact of FUDR on SMA phenotypes seen in the intestinal smn-1 KO. We found that FUDR acts on RNA to some capacity and causes lifespan extension of the intestinal KO. Through further experimentation we hope to uncover how organisms cope with stress, via the IPR, as it relates to SMN deficiency in the intestine and how FUDR acts on RNA when smn-1 is absent in the intestine.
Degree Date
Spring 5-11-2024
Document Type
Thesis
Degree Name
M.S.
Department
Biology Department
Advisor
Adam Norris
Second Advisor
Richard Jones
Third Advisor
Alejandro D'Brot
Number of Pages
49
Format
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License
Recommended Citation
Philips, Lindsey, "The Tissue-Specific Role of smn-1 in C. elegans" (2024). Biological Sciences Theses and Dissertations. 27.
https://scholar.smu.edu/hum_sci_biologicalsciences_etds/27
