Emily Lavering

Mentor: Daniel Weeks, PhD

Year Entered Into Program: 2018

PhD Institution: University of Iowa, 2023

Affiliations

  • Department of Biochemistry

Research Description

The Functional Roles of Protein Aggregation: Establishing Nucleolar Architecture

Protein aggregation is the hallmark of diseases such as Huntington’s and Parkinson’s diseases, but recent research has established protein aggregation as essential to many cellular processes as it aids in cellular organization and spatial control of protein distribution. Many of the proteins involved in ribosome biogenesis form aggregates. Ribosome biogenesis can be described by three general, sequential processes: synthesis of components, rRNA modification, and ribosome assembly. Our objective is to map the distribution of aggregating proteins involved in ribosome biogenesis to the domains of the nucleolus to understand how aggregation may aid the sequential process of ribosome biogenesis. We are also interested in the state of the aggregation of these proteins under normal conditions, and how they change when rRNA production is inhibited. We hypothesize that 1) ribosome biogenesis proteins involved in similar steps of the process will aggregate together, sharing nucleolar domains, and 2) the equilibrium of the aggregation phase will be altered when rRNA production stops. We are testing our hypothesis by making fluorescent protein fusions to observe the aggregation in Xenopus laevis embryos and oocytes, and by using reagents such as thioflavin T and hexanediol to determine the state of aggregation. Recent studies suggest that the nucleolus is a site where both useful and pathological protein aggregation is regulated, which makes these studies instructive for multiple aggregate based diseases.

Awards

  • Fellowship appointment on the Pharmacological Sciences Training Program (NIH T32 GM067795), University of Iowa, 2019-2021

Publications

  1. Powers, K.T., Lavering, E.D., and Washington, M.T.:  Conformational Flexibility of Ubiquitin-Modified and SUMO-Modified PCNA Shown by Full-Ensemble Hybrid Methods. Journal of Molecular Biology, 430(24): 5294-5303, 2018.  PMCID: PMC6453135

Research