# The function of germ granules in maintaining pluripotency in the C. elegans germline

> **NIH NIH R01** · MOUNT DESERT ISLAND BIOLOGICAL LAB · 2022 · $332,000

## Abstract

Project Summary
 Germ cells and somatic cells from an individual carry identical copies of DNA; yet, only germ cells have
the potential to give rise to all the cell types of each subsequent generation. This suggests that epigenetic factors
confer pluripotent and immortal potential to germ cells. Some of these epigenetic factors are exclusive to the
germ cell cytoplasm, and in certain cases their presence is enough to reprogram somatic nuclei to restore
pluripotency and immortal potential. A distinguishing feature of germ cell cytoplasm are germ granules. Germ
granules are a phase-separated, heterogeneous mix of RNA and protein that have been observed in the germline
of most animals. Because core germ-granule composition is conserved from nematodes to humans, the
genetically tractable model C. elegans is used to study how germ granules function to regulate the pluripotent
and immortal potential of germ cells. Germ granules extend the environment of the nuclear pore into the
cytoplasm, where they serve as a safety next to ensure that nascent transcripts coming from the nucleus are
licensed for germline expression. Depletion of germ granules in C. elegans causes sterility and germ-to-soma
transformation. The long-term objectives of this research are to understand how germ granules regulate cellular
pluripotency and their potential to be manipulated to induce pluripotency when it is needed (e.g. regeneration)
or shut it off when it is not (e.g. cancer).
 A conserved core of germ-granule proteins act as multipotency factors, and are often repurposed in the
soma during development, tissue regeneration, and tumorigenesis. This core consists of Vasa DEAD-box RNA
helicases, small RNA binding Argonaute proteins, and LOTUS-Tudor domain proteins that interface and
stimulate Vasa and Argonaute activity. The role of these multipotency factors during tumorigenesis, and whether
they contribute to the phenomenon of cancer/testis (CT) antigen expression in various tumors has not been
explored. Here, C. elegans is used to understand how these core proteins are expressed and distributed, what
they interact with, and their role in fertility and developmental plasticity. The specific aims in this proposal look
at 1) the role of germ granules in protein expression and turnover, primarily focusing on the novel interaction of
GLH/Vasa with PCI scaffolding complexes, 2) how GLH promotes the differential translation of spermatogenic
transcripts, and 3) how GLH and a new LOTUS-Tudor protein called LOTR-1 cooperates to maintain germline
integrity. If successful, these findings will reveal novel ways to manipulate cellular pluripotency and expose the
potential therapeutic targets that directly regulate the cytoplasm instead of nuclear gene expression networks.

## Key facts

- **NIH application ID:** 10371247
- **Project number:** 5R01GM113933-08
- **Recipient organization:** MOUNT DESERT ISLAND BIOLOGICAL LAB
- **Principal Investigator:** Dustin Lynn Updike
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $332,000
- **Award type:** 5
- **Project period:** 2015-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10371247

## Citation

> US National Institutes of Health, RePORTER application 10371247, The function of germ granules in maintaining pluripotency in the C. elegans germline (5R01GM113933-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10371247. Licensed CC0.

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