Characterizing Nucleophosmin (Npm1) and heterologous aggregates in the budding yeast S. cerevisiae

Protein aggregation is a biological feature akin to fire – it is very important, but dysregulation causes death and destruction. Cells prevent and correct improper protein aggregation with a class of proteins, termed molecular chaperones, and membraneless compartments, termed protein quality control centers (PQCs). Recent studies have implicated the animal nucleophosmin (Npm1) protein as a molecular chaperone involved in the formation of PQCs. Many diseases, including Huntington’s Disease and various cancers, are linked to aggregation and the mis-regulation of Npm1. However, the precise mechanisms of Npm1 in regulating protein aggregation are not well understood. To learn more about Npm1 and to better understand its role in regulating inappropriate protein aggregation would reveal novel information about Npm1 and its role in disease.

I introduced the NPM1gene into the experimentally facile model organism, baker’s yeast, or S. cerevisiae. Yeast are single-celled organisms which are easy to manipulate at the genetic and molecular levels. Yeast lack Npm1 but have many chaperones and PQC mechanisms in common with animals. I found that the version of Npm1 I expressed in yeast cells responds to stress conditions and possibly regulates protein aggregation. Although my results with Npm1 and protein aggregation are not yet conclusive, the yeast model described here could facilitate subsequent research in higher-order organisms and/or drug development, which would ultimately be applicable to human health and disease.