Open Access. Powered by Scholars. Published by Universities.®

Biochemistry, Biophysics, and Structural Biology Commons

Open Access. Powered by Scholars. Published by Universities.®

Articles 1 - 2 of 2

Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Ipsc Based Gene Correction And Disease Model Of A New Class Of Lgmd Due To Poglut1 Mutation, Jose Ortiz-Vitali Aug 2019

Ipsc Based Gene Correction And Disease Model Of A New Class Of Lgmd Due To Poglut1 Mutation, Jose Ortiz-Vitali

UT GSBS Dissertations and Theses (Open Access)

Recently, a novel class of muscular dystrophy has been discovered in a family due to autosomal recessive missense mutation in POGLUT1. Mutation of this enzyme leads to decreased O-glucosyltransferase activity and impaired Notch signaling, the pathways important for skeletal muscle stem cell (satellite cells) quiescence and activation. We hypothesize that reduced POGLUT1 activity and impaired Notch signaling is causative of this limb girdle muscular dystrophy through dysfunction of muscle stem cells and myogenic progenitors.

To test this, we have used iPSCs for disease modeling and rescue experiments. Using a CRISPR based gene targeting method, we aimed to correct the point ...


Thiol-Based Misfolding: Linking Redox Balance To Cytosolic Proteostasis, Ford Amy May 2019

Thiol-Based Misfolding: Linking Redox Balance To Cytosolic Proteostasis, Ford Amy

UT GSBS Dissertations and Theses (Open Access)

The eukaryotic cytosolic proteome is vulnerable to changes in proteostatic and redox balance caused by temperature, pH, oxidants and xenobiotics. Cysteine-containing proteins are especially at risk as the thiol side chain is subject to oxidation, adduction and chelation by thiol-reactive compounds. All of these thiol-modifiers have been demonstrated to induce the heat shock response and recruit protein chaperones to sites of presumed protein aggregation in the budding yeast Saccharomyces cerevisiae. However, endogenous targets of thiol stress toxicity responsible for these outcomes are largely unknown. Furthermore, I hypothesize proteins identified as redox-active are prone to misfolding and aggregation by thiol-specific stress ...