Protein misfolding and aggregation has been implicated in a broad range of devastating human diseases including Alzheimer's, Parkinson's and Huntington's. While protein folding has been studied extensively in vitro, most biophysical techniques require a purified system and cannot be employed in vivo. Therefore, our understanding of the factors governing protein folding within the cellular context is limited. Usin our unique fold or die genetic selection, a powerful tool we can use to evolve a better in vivo protein folding environment, we have discovered the protein OsmY as upregulated in many of our folding enhanced strains. Excitingly, OsmY is unlike any previously described chaperone and potentially represents a new class of protein folding helpers. In this proposal, we seek to characterize this new chaperone using a combination of in vivo and in vitro techniques to better understand the role of OsmY in cellular protein stability.
Understanding the fundamental aspects controlling protein folding and stability in vivo is critical to treating wide range of human diseases. Through employing a novel genetic selection in E. coli, which forces the cell maintain an unstable, aggregation prone protein in order to survive, we have discovered the previously uncharacterized molecular chaperone OsmY. This proposal herein seeks to understand the role of this novel chaperone in cellular protein folding and stability.