Dr. Harry Orr

Lab Medicine & Pathology
Medical School
Twin Cities
Project Title: 
Neural Degenerative Disease-Caused Spinocerabellar Ataxia 1

Spinocerebellar Ataxia type 1 (SCA-1) disease is caused by a CAG repeat that encodes a polyglutamine tract in Ataxin-1. Previous studies demonstrate a gain-of-function mechanism underlies this disease. The glutamine expansion alters its interactions with capicua and RBM17, regulators of RNA transcription and splicing, respectively. Successful RNA-seq projects have identified significant changes in RNA transcription and splicing between healthy and diseased mice. Recently, these researchers have demonstrated the ability to deliver an artificial oligonucleotide that knocks down Ataxin-1 RNA levels concomitantly reducing protein levels, significantly reducing the disease phenotype. They have created and are creating new mouse models to identify and group transcriptome changes via RN-seq. The researchers will use this information to continue their search for influenced pathways and identify transcriptional regulatory sequences. During 2020, several new models will be sent for RNA-seq and will need to be analyzed and compared to the existing datasets. This will continue to refine the understanding of SCA-1. The University of Minnesota Genomics Center will perform RNA-seq. MSI staff assist with bioinformatics analysis and support and MSI resources are used for data storage and analysis. The software MacVector and Sequencher are used to design qPCR targets found in the RNA-seq data; MacVector is used during routine molecular biology.

Project Investigators

Lisa Duvick
Hillary Handler
Dr. Christy Henzler
Ham Ching Lam PhD
Brennon O'Callaghan
Dr. Harry Orr
Orion Rainwater
Kevin Silverstein PhD
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