Investigating the Role of Extracellular scl Genes in TDP-43-Mediated Neurotoxicity in C. elegans

Location

Poster #3

Start Date

1-5-2026 12:00 PM

Department

Biology

Abstract

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder that primarily affects motor neurons. In ALS, TDP-43, a nuclear RNA-binding protein, becomes misfolded and forms aggregates within cells. These aggregates can spread from one neuron to another through the extracellular matrix (ECM), a dynamic and complex structure that provides support to tissues and cells. ECM remodeling is regulated by proteases that degrade matrix components, facilitating development, repair, and disease progression. To investigate the contributions of the ECM to the spread of misfolded proteins in ALS, we use the nematode Caenorhabditis elegans, a transparent and genetically tractable model organism. Using a genetic approach, a deletion of an ECM gene from the scl gene family will be introduced into a TDP-43 transgenic line. Using well characterized behavioral assays, the movement of these strains will be examined to assess the impact of the scl-10 gene on TDP-43-related toxicity. These findings may support remodeling of the ECM as a possible therapeutic strategy for the treatment of ALS pathology.

Faculty Sponsor

Cindy Voisine

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May 1st, 12:00 PM May 1st, 1:30 PM

Investigating the Role of Extracellular scl Genes in TDP-43-Mediated Neurotoxicity in C. elegans

Poster #3

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder that primarily affects motor neurons. In ALS, TDP-43, a nuclear RNA-binding protein, becomes misfolded and forms aggregates within cells. These aggregates can spread from one neuron to another through the extracellular matrix (ECM), a dynamic and complex structure that provides support to tissues and cells. ECM remodeling is regulated by proteases that degrade matrix components, facilitating development, repair, and disease progression. To investigate the contributions of the ECM to the spread of misfolded proteins in ALS, we use the nematode Caenorhabditis elegans, a transparent and genetically tractable model organism. Using a genetic approach, a deletion of an ECM gene from the scl gene family will be introduced into a TDP-43 transgenic line. Using well characterized behavioral assays, the movement of these strains will be examined to assess the impact of the scl-10 gene on TDP-43-related toxicity. These findings may support remodeling of the ECM as a possible therapeutic strategy for the treatment of ALS pathology.