# Spatiotemporal Regulation of Liquid-like Condensates in the Germline

> **NIH NIH R01** · HARVARD MEDICAL SCHOOL · 2022 · $361,558

## Abstract

SUMMARY/ABSTRACT
 Liquid droplet organelles (also referred to as liquid-like condensates) are dynamic concentrations of
protein and RNA that coalesce spontaneously from the cytoplasm or nucleoplasm via liquid-liquid phase
transition. Like oil and water, these liquid droplets and their surrounding cytoplasm are thought to co-exist as
separate states of liquid. Current models posit that liquid droplet organelles may exist to concentrate reactants
together in space and time in ways that facilitate biochemical reactions such as the complexes processes that
underlie gene regulation. Eukaryotic cells possess many non-membrane-enclosed liquid droplet organelles
including nucleoli, processing bodies, cajal bodies and germ granules. Germ granules are found in the germ
cells of all/most animals where they are thought to contribute to germ cell totipotency. Indeed, orthologous
proteins (e.g. VASA) are found in germ granules of many different species of animals, hinting that some aspects
of germ granule function may be conserved in all animals.
 Most epigenetic information is erased at or near the start of each new generation in animals to ensure
totipotency of the germline. In some cases, epigenetic information escapes reprogramming and is passed from
parent to offspring. The inheritance of epigenetic information for more than one generation is termed trans-
generational epigenetic inheritance (TEI). Small non-coding RNAs (e.g. siRNAs, miRNAs, piRNAs, and tRNA
fragments) have emerged as important mediators of TEI (cumulatively, RNA-directed TEI). dsRNA-mediated
gene silencing (RNAi) in C. elegans is a robust and dramatic example of RNA-directed TEI. My lab is using RNAi
inheritance in C. elegans as a model system to explore how epigenetic signals are passed across generations
in animals. We recently conducted a genetic screen for RNAi inheritance factors that identified two conserved
RNA binding proteins (RBPs). These RBPs contribute directly to inheritance by helping to maintain the
expression of silencing RNAs over generations during RNAi inheritance. Interestingly, both RBPs localize to a
new C. elegans germ granule whose biogenesis is developmentally regulated and whose positioning relative to
other germline condensates is highly ordered. Finally, we find that the two RNAi inheritance factors we have
identified are required for maintaining germline immortality. Together, our results have led us to propose that the
temporal and spatial ordering of liquid droplet organelles may help germ cells organize and coordinate the
complex RNA processing pathways underlying gene regulatory systems, such as RNA-directed TEI and germline
immortality. This proposal outlines our efforts to further understand how liquid-like condensates form during
development, how they assemble into complex structures with other germline condensates, and, most
importantly, why they do so.

## Key facts

- **NIH application ID:** 10361464
- **Project number:** 5R01GM132286-04
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Scott G Kennedy
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $361,558
- **Award type:** 5
- **Project period:** 2019-06-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10361464

## Citation

> US National Institutes of Health, RePORTER application 10361464, Spatiotemporal Regulation of Liquid-like Condensates in the Germline (5R01GM132286-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10361464. Licensed CC0.

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