Joseph, JerelleMerghoub, Safaa2024-07-232026-09-292024-07-232026-09-292024-052024-07-23http://arks.princeton.edu/ark:/88435/dsp01pn89d9962https://theses-dissertations.princeton.edu/handle/88435/dsp01pn89d9962TDP-43 has been shown to be a key driver of aberrant condensate formation in cells, resulting in various diseases such as ALS, FTD, and in cancer. While much research has been done to show the relationship between TDP-43 accumulation and development of disease, much is not yet understood about the mechanisms that govern the formation of the protein aggregates. Using computational techniques and principles from biology and chemistry, the objective of this project is to measure aggregation kinetics and describe the behavior of abnormal proteins that give rise to serious illnesses afflicting a large part of the global population. With a characterization of the sequences that give rise to aggregation, it was possible to measure the efficacy of potential small molecule therapies. The work presented here demonstrates limitations in our ability to accurately detect regions of aggregation in a protein, but presents evidence that mitoxantrone is a promising small molecule that can inhibit aggregation of TDP-43.application/pdfenPrinceton University Senior Theses