Organic Chemistry Seminar

During their lifetimes, individuals commonly experience transient changes in gene expression as a result of different environmental stimuli. These responses are classically thought to have little heritable influence once they decay. However, we have recently discovered that such stimuli frequently induce self-perpetuating changes in protein conformations. This occurs most commonly in proteins that regulate information flow: chromatin modifying enzymes, transcription factors, and RNA binding proteins. These self-templating changes in protein conformation can be broadly defined as prions, although their structures do not usually match the cross-beta sheet amyloids of the archetypical prion PrP. However, like known prions, corresponding changes in protein function are heritable from one generation to the next without any change to the genome. In this sense, such protein-based inheritance represents an extreme form of epigenetics. We have begun to characterize the biochemistry of these epigenetic elements and investigate their influence on disease, development, and evolution. Lessons learned provide insight into mechanisms of pathological and beneficial protein aggregation alike, and how they might be modulated therapeutically.