Northwestern Events Calendar

Nov
1
2019

"Genome-wide in vivo CNS Screening for Modifiers of Mutant Huntingtin Toxicity"

When: Friday, November 1, 2019
12:00 PM - 1:00 PM  

Where: Ward Building, 303 E. Chicago Avenue, Chicago, IL 60611 map it

Audience: Faculty/Staff - Student - Post Docs/Docs - Graduate Students

Contact: Donna Daviston   312.503.1687

Group: Department of Physiology Seminars

Category: Lectures & Meetings

Description:

The department of Physiology welcomes Myriam Heiman, Ph.D.

Unbiased in vivo genome-wide genetic screening is a powerful approach to identify novel molecular mechanisms, but such screening has not been possible to perform in the mammalian central nervous system (CNS). Here we report the results of the first genome-wide genetic screens in the CNS using both shRNA and CRISPR libraries. Our screens identify many classes of CNS neuronal essential genes, and demonstrate that CNS neurons are particularly sensitive not only to perturbations to synaptic processes, but also autophagy, proteostasis, mRNA processing, and mitochondrial function. These results reveal a molecular logic for the common implication of these pathways across multiple neurodegenerative diseases. To further identify disease-relevant genetic modifiers, we applied our screening approach to two mouse models of Huntington’s disease (HD). Top mutant Huntingtin toxicity modifier genes included both known and novel modifier genes, results that reveal new HD therapeutic target pathways.

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