# Small molecule signaling in C. elegans

> **NIH NIH R35** · BOYCE THOMPSON INST FOR PLANT RESEARCH · 2022 · $593,590

## Abstract

Project Summary
The nematode Caenorhabditis elegans is one of the most important model organisms for biomedical
research, because of its biological tractability and because many of its physiological pathways show
strong analogies to corresponding pathways in humans. The goal of this project is to complement the
highly developed genomics and proteomics of C. elegans with a comprehensive structural and
functional characterization of its metabolome, which has been explored to only a very limited extent.
In recent work we have shown that C. elegans utilizes small-molecule architectures of unanticipated
diversity and complexity in endocrine and exocrine signaling that control almost every aspect of its life
history, including development, aging, stress resistance, and a wide range of behaviors.
One major focus of our investigations will be the elucidation of the biosynthesis and perception
mechanisms of newly identified small molecule signals that control development and aging, which will
reveal how metabolism and conserved signaling pathways interact to control life history. Of particular
interest will be the role of the potent developmental accelerator and dauer-antagonist nacq#1,
representative of a new class of C. elegans developmental regulators, and the biosynthesis and mode
of action of ascarosides that regulate C. elegans lifespan, in part via modulating steroid hormone
production. A second focus forms the identification of ligands of orphan nuclear hormone receptors
that are homologs of mammalian steroid receptors (e.g. liver-X receptor and vitamin-D receptor) and
mediate development and lifespan downstream of the perception of nacq#1 and ascarosides. Central
to the proposed research is the use of synthetic derivatives and molecular probes of the identified
signaling molecules for chemical genetic screens, as well as HPLC-MS-based methodology
("comparative metabolomics") that permits correlating spectroscopic features representing yet
unknown small molecules directly with a specific genetic background, which greatly accelerates
compound identification and their functional annotation.
Successful conclusion of this project will provide a partial structural and functional annotation of the C.
elegans metabolome, substantially increasing our understanding of conserved pathways that control
development, aging and metabolism of C. elegans and corresponding disease-relevant pathways in
mammals. The small-molecule knowledge generated will not only enable future efforts aimed at more
varied chemical genetic screens exploring additional aspects of the biology and ecology of C. elegans,
but also of nematode species relevant in agriculture or medicine. Furthermore, methodology
developed for characterizing C. elegans signaling molecules will facilitate similar studies toward
structural and functional characterization of small molecule metabolites from other model organisms.

## Key facts

- **NIH application ID:** 10375378
- **Project number:** 5R35GM131877-04
- **Recipient organization:** BOYCE THOMPSON INST FOR PLANT RESEARCH
- **Principal Investigator:** Frank Clemens Schroeder
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $593,590
- **Award type:** 5
- **Project period:** 2019-05-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10375378

## Citation

> US National Institutes of Health, RePORTER application 10375378, Small molecule signaling in C. elegans (5R35GM131877-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10375378. Licensed CC0.

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