# An analysis of the regulation and functions of a novel family of membraneless organelles in eukaryotic cells

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2021 · $377,179

## Abstract

The eukaryotic cell is a highly compartmentalized structure that is subdivided into discrete functional areas by
the presence of a variety of membrane-enclosed organelles. This segregation of functions is essential for
normal cell growth and survival. Interestingly, recent studies have indicated that additional levels of
compartmentalization exist within these cells. In particular, a number of cytoplasmic granules that contain
distinct sets of proteins and mRNAs have been identified. Two of the best-characterized of these
ribonucleoprotein (RNP) structures are the Processing-body (P-body) and stress granule. These granules differ
from the more traditional organelles in that they lack a limiting membrane and are rather dynamic in nature.
These granules are evolutionarily conserved and have been linked to a number of human diseases, including a
variety of cancers and neurodegenerative disorders. However, despite these observations, the physiological
functions of these RNP structures remain poorly understood. This lack of understanding represents a critical
gap in our current knowledge and attempting to bridge this divide is a primary research focus in our lab.
 The experiments in this proposal aim to further our understanding of both the biological roles of these
RNP granules and the mechanisms that regulate their assembly. The first two aims come at this question of
biological function from different directions. In the first, we will assess the physiological consequences of
having key signaling proteins associate with the P-body and/or stress granule during conditions of stress. Our
focus here is on particular protein kinases and the possibility that this re-localization to RNP granules allows for
a rewiring of the signaling networks present in the cell. In the second, we focus on the granule as a whole and
ask how cell physiology is altered in mutants that lack these RNP structures. These latter studies focus on a
potential role in protein homeostasis that was suggested by recent work from our lab. In particular, we have
found that mutants lacking P-bodies exhibit elevated levels of protein misfolding and aggregation. The
experiments here aim to determine the underlying mechanisms responsible for these effects and should
establish whether these RNP granules have a direct role in the maintenance of protein quality control (PQC).
Finally, the third aim examines several key aspects of the regulation and assembly of P-body foci. In particular,
the studies will define the molecular mechanism underlying PKA-mediated control of P-body assembly and
develop a facile method for the purification of these RNP granules. The three specific aims of the proposal are
as follows: (1) determine the physiological consequences of protein kinase recruitment to RNP granules; (2)
define the underlying mechanisms responsible for the P-body-mediated effects on PQC; and (3) examine the
process and regulation of P-body assembly.

## Key facts

- **NIH application ID:** 10135112
- **Project number:** 5R01GM128440-04
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Paul K Herman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $377,179
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10135112

## Citation

> US National Institutes of Health, RePORTER application 10135112, An analysis of the regulation and functions of a novel family of membraneless organelles in eukaryotic cells (5R01GM128440-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10135112. Licensed CC0.

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