Final Report Summary - DARKSIDE (Harnessing the Dark Side of Protein Folding: Manipulating Aggregation for Recombinant Protein Production)
During the course of this project, we were indeed able to illuminate several novel mechanisms regulating protein expression in response to stress, particularly metabolic stress. We characterized a mechanism for targeting manifolded proteins to aggregates, as well as a beneficial survival mechanism that exploits the aggregation property of some proteins to facilitate cell recovery from stress.
The completion of this project has created several novel methodologies and resources for the yeast community, including effective BioID in yeast, and efficient modular chromosomal integration of vectors. In addition to the progress that we have made in understanding the active aggregation pathways in yeast, we have also uncovered a novel mechanism that can be exploited to control the metabolism of yeast used for recombinant protein production. Finally, beyond the scope of the project, this metabolic regulation by functional protein aggregates open new avenues for studying neurodegenerative diseases.