Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease marked by dysfunction and degeneration of motor neurons, leading to loss of innervation and subsequent muscle atrophy. There is no cure for ALS, and the two medications available for treatment show limited results. The cause of ALS, and the molecular mechanisms that underlie related cell death, remain unknown. The leading hypothesis in the field is that ALS-linked neural degeneration occurs due to misfolding and aggregation of one or more prion-like proteins within motor neurons, and that the spread of these aggregates causes disease propagation. Patient studies have led to the identification of ALS- linked mutations in several proteins, including Fused in Sarcoma (FUS) and TAR-DNA Binding Protein (TDP-43). FUS and TDP-43 are RNA/DNA binding proteins that have been implicated in increased protein aggregation and subsequent cellular degeneration in ALS suffers. Students enrolled in NEUR474: Neurodegenerative Diseases used site-directed mutagenesis to generation mutant variants of FUS and TDP-43 that mimic mutations found in diagnosed populations. Mutations were confirmed by Sanger sequencing, and the altered coding sequence was subcloned into a mammalian expression vector for transfection into motor neuron like cell line NSC-34. Changes in neurite structure and viability was measured over several days via in-incubator live cell microscopy. Students in this poster session will share their individual results within the context of the existing scientific literature on their chosen mutant. This project is a part of the ongoing research conducted in the Kaur lab.
Student Names Boone, Jacob D., Goudreau, Helen L. Chiavarini, Nicole S., Kopocs, Calae C. Founds, Michael W. Garris, Rosanna L. Gonzalez, Tatiana E. Granade, Lucas, Hartzell, Jack S. Henken, Hannah J. Kerkenbush, Zachary L. Krupp, Lily K., Washburn, Lauren A. Middlesworth, Harris P., White, Ashley M. Salinas, Ricardo Zopfi, Mikayla L.
