# Molecular Genetic Analysis of Extracellular RNAs in C. Elegans

> **NIH NIH R01** · HARVARD UNIVERSITY · 2021 · $392,504

## Abstract

Project Summary
Siblings resemble each other more than expected based on the genes that they inherit from their parents. This
unexpected finding derives from recent studies that measure the association between genotype (variations in
DNA sequence) and traits (e.g. height or disease risk) among large populations of unrelated people. This
discrepancy indicates that parents may transmit extra, non-gene, information to their offspring. This non-gene
information is called epigenetics, literally “beyond” genetics, and is a well-established field, but convention
accepts that epigenetic information is erased each generation. Studies in the emerging field of
transgenerational epigenetic inheritance (TEI) are challenging this convention. However, little is known
about how inherited epigenetic information is encoded, how it responds to environmental conditions, and how it
is transmitted between generations. Because inherited epigenetic information is malleable and may account for
up to half the inheritance of disease risk, the answers to these questions will have an enormous impact on
society and medicine.
 Investigating how TEI is established, maintained, and transmitted is challenging: it requires analysis of
multiple generations and studies to date indicate that its effects are impermanent, fading with successive
generations. The proposed research uses the nematode C. elegans to investigate TEI. C. elegans has
numerous experimental advantages for studying TEI, primary among them is a fast, three-day, generation time
and a powerful molecular tool called RNA interference (RNAi), which can direct the silencing of any gene. One
special characteristic of RNAi in C. elegans is that the silencing signals, a form of RNA, can move between
cells and tissues, including to the germline, thus transmitting silencing to future generations. Published studies
from the applicants group characterized an RNAi-dependent mechanism of TEI, showing that epigenetic
silencing could be maintained for nearly 20 generations. To further explore the transmission of TEI in C.
elegans the applicant proposes (Aim 1) to investigate the activity and selectivity of proteins that transport RNA
between cells; (Aim 2) to characterize the biogenesis and transport of endogenous mobile RNAs and to
investigate their role in epigenetic inheritance; and (Aim 3) to investigate the prevalence, mechanisms, and
utility of TEI for organismal adaption to environmental change.

## Key facts

- **NIH application ID:** 10160923
- **Project number:** 5R01GM089795-12
- **Recipient organization:** HARVARD UNIVERSITY
- **Principal Investigator:** CRAIG Patrick HUNTER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $392,504
- **Award type:** 5
- **Project period:** 2009-09-30 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10160923

## Citation

> US National Institutes of Health, RePORTER application 10160923, Molecular Genetic Analysis of Extracellular RNAs in C. Elegans (5R01GM089795-12). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10160923. Licensed CC0.

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