Yun Tang- defense: "Characterization of Mouse Model of Aging and Alzheimer’s Disease using Protein Stability Measurements

Characterization of Mouse Model of Aging and Alzheimer's Disease using Protein Stability Measurements

A recently developed suite of mass spectrometry-based proteomic methods allows for the large-scale evaluation of protein folding stability. These techniques employ chemical or thermal denaturation approaches (such as SPROX and TPP) as well as proteolysis strategies (including DARTS, LiP, and PP) to assess protein stability. While these methods have been proven effective for protein target discovery, there is still limited understanding of the relative strengths and weaknesses of each technique when it comes to characterizing biological phenotypes. Therefore, in this dissertation, it first presents a comparative study of SPROX, TPP, and LiP in characterizing different phenotypes to fully evaluate these techniques. These methods were then be used to explores the development and progression of AD in the mouse model. Both female and male mouse models were used to explore the similarities and differences in AD progression across genders. The ultimate goal of this work is to identify novel disease biomarkers and potential drug targets, as well as elucidating molecular mechanisms underlying stability change.