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Examination of Metabolism and Cellular Health in a Saccharomyces cerevisiae Model for TPI Deficiency

Triosephosphate isomerase (TPI) is a well studied protein that plays a role in glycolysis and can be found in almost every living cell. TPI deficiency is a rare genetically inherited disease associated with progressive neurological dysfunction and childhood death. However, not much is known about how the disease causing mutations affect metabolism and cellular health. This project examines mutant TPI alleles that have been shown to cause neurodegeneration in both Drosophila melanogaster and Homo sapiens. This study characterized the cell growth rates, protein stability and metabolic activity of yeast each expressing one of six mutant D. melanogaster TPI alleles. Previous research on TPI has shown that the enzyme demonstrates a high degree of structural and functional similarity across species. As TPI function and structure are highly conserved among organisms, studying D. melanogaster TPI in yeast cells can provide more information about how the expression of the mutant alleles in humans may lead to neurodegeneration.