Developing Tools to Discern How Mutations Impact Protein Homeostasis

Protein homeostasis can be defined as the steady state level of functional proteins in the cell. This level depends on processes that affect protein gain (transcription and translation) and loss (degradation, misfolding, and aggregation). Mutations, changes to the DNA sequence that codes for a given protein, can affect one (or more) of these processes. Understanding how mutations affect each these processes has implications for medicine as many diseases are caused by mutations that disrupt protein homeostasis. Investigating how individual mutations affect each of the individual processes involved in protein homeostasis will enable improved design strategies for treating diseases caused disrupted protein homeostasis. To that end, we have developed a preliminary tool called PDR (Production Degradation Reporter) that can separate the impacts individual mutations have on the production and degradation of a protein of interest in cells. While we have seen preliminary success with the current design, we are interested in exploring alternative designs for this tool.