Investigation into the Dictyostelium protein quality control network

Medical College Of Wisconsin, Milwaukee WI

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Abstract

7. Project Summary A hallmark of many neurodegenerative diseases is the formation of large protein aggregates, leading to neuronal dysfunction and cell death. Protein aggregation results from the accumulation of misfolded proteins, leading to an imbalance in protein homeostasis. A major question is how do cells recognize and deal with misfolded proteins? Thus, insight into mechanisms responsible for preventing protein aggregation would be beneficial. Serendipitously, we found that the model organism Dictyostelium discoideum normally express proteins with long polyglutamine tracts that cause one class of neurodegenerative diseases. Recently, I showed that Dictyostelium have an extraordinary ability to resist aggregation of a polyglutamine-expanded protein known to aggregate and cause disease. Here, I propose to investigate mechanisms utilized by Dictyostelium to resist polyglutamine aggregation and explore novel aspects of the Dictyostelium protein quality control network.