# Genetic Analysis of Nematode Egg Laying and Co-regulated Behavioral Systems

> **NIH NIH R01** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2020 · $383,585

## Abstract

PROJECT SUMMARY/ABSTRACT
The long-term objective of this project is to understand how genes specify the development and functioning
of a behavioral system. The anatomically simple neuromuscular system of the nematode Caenorhabditis
elegans consists of diverse types of neurons and muscles while being sufficiently small and simple to allow
a complete description of its cells, neural circuits and cell lineage, facilitating the identification of anatomical
and developmental abnormalities caused by mutations. Studies of the C. elegans egg-laying system and of
the neuromuscular systems that control behaviors coordinately regulated with egg laying, such as feeding
behavior, offer opportunities for the analysis of a broad variety of fundamental biological problems of
relevance to many human disorders. The major issue that this project will address is how C. elegans
responds behaviorally to oxygen stresses, as oxygen is essential for animal life but also can be damaging to
tissues and cause disease. This project will analyze how two distinct oxygen stresses -- oxygen deprivation
and reactive oxygen species – induce aversive behavioral responses. First, what are the molecular
mechanisms that mediate behavioral responses to oxygen deprivation, which profoundly affects cellular and
organismic physiology and is responsible for the cardiac damage in heart attacks as well as for disorders of
the kidneys, nervous system and other organs? The major pathway that mediates responses to chronic
oxygen deprivation has been implicated in many human disorders and has defined major therapeutic targets
for cancer. This aim will identify new components of this important pathway, including potential new drug
targets and drug leads, and also reveal how this pathway controls animal physiology and behavior. Second,
how do reactive oxygen species cause the neural circuits of the C. elegans feeding organ, the pharynx, to
reverse phayngeal pumping actions to drive spitting instead of feeding, thereby preventing the ingestion of
toxic oxygen species? The C. elegans pharyngeal nervous system is the simplest known and longest-
studied connectome in biology, yet much about how it functions remains unknown. Connectomics, the study
of nervous-system connectivity maps, promises critical insights into human brain organization and function,
is a major theme of the NIH BRAIN Initiative and is crucial for our understanding of many neurologic and
neuropsychiatric disorders. However, an anatomical connectome is insufficient to reveal how the nervous
system drives behavior. This aim will comprehensively probe the circuit, cellular, and molecular properties
by which the pharyngeal nervous system responds to reactive oxygen species, relate these properties to the
simplest and most completely defined connectome in biology and reveal the types of information needed to
complement a connectome to establish how a nervous system drives behavior.

## Key facts

- **NIH application ID:** 9939606
- **Project number:** 5R01GM024663-43
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** H ROBERT HORVITZ
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $383,585
- **Award type:** 5
- **Project period:** 1978-01-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9939606

## Citation

> US National Institutes of Health, RePORTER application 9939606, Genetic Analysis of Nematode Egg Laying and Co-regulated Behavioral Systems (5R01GM024663-43). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9939606. Licensed CC0.

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