# The Role of Chromatin in Metabolic Homeostasis

> **NIH NIH R35** · STANFORD UNIVERSITY · 2021 · $468,738

## Abstract

The coordination of cellular function with the environment is essential for adaptation and survival. Dynamic
nutrient environments are ubiquitous throughout nature and include competitive growth environments of
proliferating microorganisms and tissue niches in multicellular organisms. Failure to adapt can lead to cell death,
developmental defects, and disease.
 Adaptive cellular responses are often achieved by rapid inducible changes in gene expression programs.
An ideal mechanism to achieve this is through modification of chromatin. Despite this knowledge, the
mechanisms by which chromatin modification contributes to metabolic plasticity remain largely unexplored. As
such, many broad biological questions remain unanswered: How do metabolic signaling pathways communicate
with chromatin to regulate gene expression? How does the metabolic environment modify chromatin to facilitate
adaptive gene expression and coordinate cell division? How do chromatin modifications influence energy
metabolism plasticity during developmental programming? How is metabolic memory propagated?
 Our proposed research is significant because it will establish chromatin modifiers as necessary
components of metabolic homeostasis, and serve as a platform to investigate epigenetic alterations and
metabolic dysfunction in developmental abnormalities and disease states. Our broad research goal is to define
the chromatin modification events that coordinate metabolic plasticity and are central to adaptive cellular
responses. Our central hypothesis is that chromatin modifiers link nutrient sensing pathways to
metabolic gene regulation required for proper fitness, proliferation, and development. We plan to
investigate this hypothesis using innovative approaches that include metabolic-synchronization, as well as
single-cell chromatin and metabolic profiling. We are ideally suited to carry out these studies, as our research
was the first to demonstrate that a chromatin remodeling complex functions downstream of metabolic signaling
pathways to regulate coordinate metabolism with cell division and developmental timing.
 Through achievement of our research goals we expect the following outcomes: Comprehensive
determination of histone modifications that are in tune with energy metabolism pathways; determination of the
relationship between nutrient sensing pathways and chromatin; characterization of the tissue-specific metabolic
requirements during development; identification of novel chromatin-mediated mechanisms for metabolic memory
and diversification. These investigations will greatly enhance our knowledge of metabolic plasticity mechanisms
and how they contribute to cellular and organismal viability, development and disease.

## Key facts

- **NIH application ID:** 10205189
- **Project number:** 2R35GM119580-06
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Ashby J. Morrison
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $468,738
- **Award type:** 2
- **Project period:** 2016-08-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10205189

## Citation

> US National Institutes of Health, RePORTER application 10205189, The Role of Chromatin in Metabolic Homeostasis (2R35GM119580-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10205189. Licensed CC0.

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