# Chromatin and metabolic regulation of plasticity in a predatory nematode

> **NIH NIH R35** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2024 · $385,000

## Abstract

PROJECT SUMMARY: The environment can elicit multiple phenotypes from a single genotype, a phenomenon
referred to as developmental (phenotypic) plasticity. Early-life environmental conditions can have lasting
consequences on adult health, such as fetal exposure to toxic chemicals or malnutrition. However, we can also
use developmental plasticity to our benefit, including learning, adaptive immunity, and the benefits of diet and
exercise. Despite the importance of plasticity for reproductive fitness and health, we still lack a mechanistic
understanding of how it works. My laboratory seeks to address this gap in knowledge by applying biochemical
methods to an organismal model of phenotypic plasticity. Evidence from my work and others points to histone
modifications as key intermediaries between diet and phenotype. The central hypothesis of our laboratory is that
the metabolic substrates of histone modifications are, in effect, the signaling molecules which relay diet to
phenotype. Identifying these pathways is necessary to understand how poor – or overly rich – diets contribute to
disease.
Historically, plasticity has been studied in non-model organisms with limited molecular tools. In contrast,
development in model organisms has traditionally focused on invariant processes in invariant conditions. In my
lab, we use an animal model that is both (1) experimentally tractable and (2) exhibits an extreme form of plasticity,
to reveal the connections between diet and phenotype. Pristionchus pacificus nematodes express one of two
possible mouth forms in adults – omnivore or bacterivore – depending on the dietary conditions they experience
as juveniles. In my postdoc, I developed P. pacificus as a model system to explore the role of chromatin in
plasticity. This work led to the discovery that histone 4 (H4) acetylation controls mouth-form development. The
research in my independent laboratory builds off of this result, and seeks to determine the molecular pathways
from diet to metabolism, and from metabolism to gene expression.
In the first five years, we will investigate the upstream metabolic signals and downstream mechanisms of gene
regulation which determine P. pacificus mouth-form. First, we will determine which metabolic pathways are
affected by diets that induce either morph. Second, we will determine how these pathways feed into histone-
modifications, hormone levels, or both. Third, we will investigate how H4 acetylation induces transcription of
genes that control mouth-form. To address these questions, we combine techniques from chromatin
biochemistry with unbiased genome-wide approaches. Our long-term goal is to apply the insight gained from
these experiments to prevent, or treat, dietary-influenced diseases in humans such as type-II diabetes, obesity,
and heart disease.

## Key facts

- **NIH application ID:** 10893422
- **Project number:** 5R35GM150720-02
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Michael S Werner
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $385,000
- **Award type:** 5
- **Project period:** 2023-07-25 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10893422

## Citation

> US National Institutes of Health, RePORTER application 10893422, Chromatin and metabolic regulation of plasticity in a predatory nematode (5R35GM150720-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10893422. Licensed CC0.

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