Genetics Colloquium: Erika Geisbrecht

Event Type
Event Date
February 27, 2019 3:30pm
Location
1441 Genetics/Biotechnology Building

Wednesday February 27th, 2019, 3:30 PM, Room 1441  Genetics/Biotech Building

Professor Erika Geisbrecht

Department of Biochemistry and Molecular Biophysics

Kansas State University 

Talk Title: Metabolic defects promote muscle degeneration in a muscular dystrophy model

Abstract: 
Mutations in the E3 ubiquitin (Ub) ligase TRIM32 result in a subtype of limb-girdle muscular dystrophy designated 2H (LGMD2H). TRIM32 is a member of the tripartite motif (TRIM) family and is required for cell differentiation, muscle physiology and regeneration, and tumor suppression. The promiscuous role of TRIM32 in multiple biological processes prevents a complete understanding of its molecular and cellular function(s) in muscle degeneration. Uncovering the muscle-specific role of TRIM32 in LGMD2H pathogenesis has proven difficult as neurogenic phenotypes, independent of LGMD2H pathology, are also present in TRIM32 KO mice. We previously established an in vivo platform to study LGMD2H using the genetically amenable Drosophila model. Inherent advantages include the structural and functional conservation of proteins and signaling pathways, less redundancy compared to mammalian models, and a genetically amenable platform to rapidly assess morphological changes in muscle structure and function. Loss of Drosophila TRIM32, encoded by the thin (tn) gene, recapitulates clinical features observed in LGMD2H patients, including impaired locomotion and muscle degeneration. In new data that will be presented, we find that loss of TRIM32 alters the metabolic maintenance of glycolytic muscles to promote disease progression. This novel role for glycolysis in the prevention of muscle may provide new avenues for treatment strategies. 

Sponsored by LOCI and the Morgridge Institute for Research