Assessing co-translational protein aggregation and the cellular factors that prevent it

Most proteins need to attain a specific structure, their native fold, to function. Since proteins are largely unstructured upon their genesis, a large portion of the cellular resources is dedicated to helping proteins reach and maintain their native fold. A major threat to this process is protein aggregation. Most proteins contain segments called Aggregation-Prone Regions (APRs) that are normally buried within the folded structure. When APRs are exposed, they tend to engage in intermolecular interactions that prevent their parent protein from folding and lead to the formation of potentially cytotoxic protein aggregates. Indeed, over thirty disorders have been associated with the aggregation of one or several protein species, and this list is expanding. 
As proteins lack structure during translation, they are likely to expose their APRs. Despite this, the process of co-translational aggregation remains heavily understudied. The proposed research is aimed at studying co-translational aggregation on a proteome-wide scale. I will determine if and where co-translational protein aggregation occurs, and deduce cellular factors specifically aimed at preventing it. Finally, I will assess if and how translation kinetics affect co-translational aggregation. This research will yield unprecedented insight into the process of co-translational aggregation, hitherto unexplored territory in the proteostasis field.