IMPACT OF EXTRACELLULAR scl GENE FAMILY IN C. elegans EXPRESSING TDP-43: UNRAVELING NEUROTOXICITY MECHANISMS
Location
Poster #2
Department
Biology
Abstract
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that primarily affects nerve cells responsible for controlling voluntary muscles. Degeneration and eventual death of neurons in the brain and spinal cord, result in muscle weakness, atrophy, and ultimately paralysis. TAR DNA-binding protein 43, TDP-43, is a nuclear protein that plays a role in regulating gene expression and RNA processing. However, in ALS and other neurodegenerative diseases, TDP-43 forms abnormal aggregates in the cytoplasm of affected neurons. We are using the nematode C. elegans, to investigate TDP-43 related neurotoxicity. C. elegans are transparent worms with a simple nervous system and are amenable to genetic manipulation. A ribosome profiling experiment on young adults that express human TDP-43 pan-neuronally and wild type animals revealed a set of differentially translated genes belonging to the scl gene family. To understand how these genes modulate TDP-43 related neurotoxicity, I will be performing genetic crosses to introduce specific scl gene deletions into TDP-43 transgenic animals. Many members of the scl gene family are not only upregulated more than 50 times in ribosome profiling data sets but specific members are also responsible for longevity and stress resistance. Manipulating scl gene family members might reveal potential therapeutic approaches to treat ALS pathology targeting TDP-43 neurotoxicity.
Faculty Sponsor
Cindy Voisine
IMPACT OF EXTRACELLULAR scl GENE FAMILY IN C. elegans EXPRESSING TDP-43: UNRAVELING NEUROTOXICITY MECHANISMS
Poster #2
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that primarily affects nerve cells responsible for controlling voluntary muscles. Degeneration and eventual death of neurons in the brain and spinal cord, result in muscle weakness, atrophy, and ultimately paralysis. TAR DNA-binding protein 43, TDP-43, is a nuclear protein that plays a role in regulating gene expression and RNA processing. However, in ALS and other neurodegenerative diseases, TDP-43 forms abnormal aggregates in the cytoplasm of affected neurons. We are using the nematode C. elegans, to investigate TDP-43 related neurotoxicity. C. elegans are transparent worms with a simple nervous system and are amenable to genetic manipulation. A ribosome profiling experiment on young adults that express human TDP-43 pan-neuronally and wild type animals revealed a set of differentially translated genes belonging to the scl gene family. To understand how these genes modulate TDP-43 related neurotoxicity, I will be performing genetic crosses to introduce specific scl gene deletions into TDP-43 transgenic animals. Many members of the scl gene family are not only upregulated more than 50 times in ribosome profiling data sets but specific members are also responsible for longevity and stress resistance. Manipulating scl gene family members might reveal potential therapeutic approaches to treat ALS pathology targeting TDP-43 neurotoxicity.