Mariana Torrente

Prions are proteins that can adopt amyloid self-replicating conformations. Prions can cause phenotype alterations that can be inherited and allow for adaptation to shifting environments. Intriguingly, the way yeast prions engage cellular pathways has been poorly characterized. Diana will explore the epigenomic landscape for the [PIN+] prion in the baker’s yeast Saccharomyces cerevisiae. [PIN+] prions are formed by a protein of unknown function, Rnq1. While [PIN+] produces no evident phenotype, it is prevalent, naturally occurring and facilitates the formation of other prions. We have uncovered exciting connections between [PIN+] and canonical epigenetic mechanisms, such as histone post-translational modifications. Building upon this finding, we now seek to uncover the mechanisms linking [PIN+] to the epigenome and to identify the genes impacted by this link. This part of the project aligns well with NanoBioNYC Focus Area II, as it will study nanoscale interfaces within complex environments relevant to biomedical contexts. Furthermore, Rnq1, like many other prion and “prion-like” proteins, carries intrinsically disordered regions, which might allow it to undergo liquid-liquid phase separation. Does Rnq1 undergo phase separation? If so, what are the sequence domain determinants for this behavior? How does phase separation relate to its prionogenic abilities and interaction with traditional epigenetic mechanisms? To answer these questions, we will test for the ability of Rnq1 to undergo phase separation and establish sequence determinants for this behavior as well as determine the impact of this behavior on prionogenic and epigenetic abilities. Supporting NanoBioNYC’s Focus Area III, studying Rnq1 amyloid and its phase separation behavior will potentially uncover biological assembly paradigms that would allow us to develop complex adaptive, metabolic systems, and functional materials.