The Computational and Systems Biology PhD Program is proud to announce the following CSB Thesis Defense:

Natasha Patel-Murray

Fraenkel Lab

Date: Friday, May 17th

Time: 11am - 12pm

Location: 16-220

Title: Understanding Neurodegenerative Disease-Relevant Molecular Effects of Perturbagens Using a Multi-Omics Approach

Abstract: The complex cellular pathways implicated in neurodegenerative diseases are not fully understood. Chemical and genetic perturbagens can probe these molecular pathways to shed insight about the diseases or potential therapeutic targets. The goal of this thesis was to profile the functional effects of perturbagens in neurodegenerative disease models using multiple omics data types and computational approaches. In the main study of this thesis, we uncover novel modes of action for small molecule compounds that promote survival in a model of Huntington’s Disease, a fatal neurodegenerative disorder. We treated cells with chemical perturbagens and collected transcriptomic, metabolomic, epigenomic, and proteomic data. Integration of these data using an interpretable network approach revealed pathways affected by the compounds, such as autophagy and bioenergetics, which we experimentally validated. In a second study related to Huntington’s Disease, we analyzed the effects of two peripheral huntingtin gene silencing techniques in mouse liver. We show that the transcriptional and metabolomic changes associated with both genetic silencing methods converge on similar cellular pathways, such as the immune response and fatty acid metabolism. As a whole, this thesis presents new insights into the functional effects of perturbagens that could impact neurodegenerative disease pathology and drug discovery.