Nancy J. Bigley (Committee Member), Katherine Excoffon (Committee Member), Shulin Ju (Advisor)
Master of Science (MS)
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by progressive degeneration of upper and lower motor neurons in the brain and spinal cord. Multiple mutations are found in some of the proteins associated with ALS, including superoxide dismutase (SOD1), fused in sarcoma (FUS) and trans-activation response DNA-binding protein (TDP-43). TDP-43 is a DNA and RNA binding protein, well conserved, and ubiquitously expressed in all tissues. TDP-43 resides in the nucleus and sometimes shuttles between nucleus and cytoplasm. Mutations in TDP-43 leads to mislocalization of TDP-43 to the cytosol where it was ubiqutinated and hyperphosphsorylated, ultimately leading to neuronal cell death. The aim of this project is to identify and compare binding partners of both wild type (WT) and mutant TDP-43 using yeast two hybrid screening (Y2H). We identified PICK1 (Protein interacting with protein C-kinase) that binds to both wild type and disease causing mutant (M337V) TDP-43. Interestingly, PICK1 also interacts with other TDP-43 mutants (D169G, Q331K, G298S, and A315T), although the affinity of interaction is weaker.
Department or Program
Microbiology and Immunology
Year Degree Awarded
Copyright 2016, all rights reserved. My ETD will be available under the "Fair Use" terms of copyright law.