# Dynamics in Eukaryotic Dormancy: Gene Expression and Aging

> **NIH NIH R35** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2022 · $418,750

## Abstract

PROJECT SUMMARY
Dormancy is a state in which virtually all intracellular activities, such as gene expression, are thought to have
(nearly) stopped. Many organisms and cells become dormant when they face dire conditions such as lack of
nutrients. Despite its ubiquity, the state of dormancy remains poorly understood and underexplored. A major
open question is which intracellular processes might still occur in dormancy, to what extent, and whether and
how they are important for surviving dormancy. This question is relevant to dormancy of microbial spores, cancer
cells, plant seeds, worms, cells in human body, and others. Microbial spores are particularly important because
many microbes in nature often exist as dormant spores rather than as vegetative cells. Many fungal spores are
of interest because they are infectious and are difficult to kill with existing drugs for unknown reasons.
 My laboratory's goal is to answer the critical question posed above for understanding dormancy. We use
the dormant yeast (Saccharomyces cerevisiae) spores as a model system for studying eukaryotic dormancy.
With dormant yeast spores, we focus on two fundamental aspects of life:
(1) Dynamics and regulation of gene expression in dormancy
(2) Dynamics and determinants of aging in dormancy
 My lab makes quantitative measurements at single-cell and genome-wide levels and combines them with
mathematical models of gene regulations. We recently discovered that yeast spores express some genes while
dormant (i.e., in water without any nutrients) and that, surprisingly, some of the expression levels can be as high
as in vegetative yeasts. To extend this discovery, we adapted an RNA-Seq-based technique to detect all freshly
made RNAs in dormant yeast spores. We discovered that dormant yeast spores transcribe ~65% of their genes,
with ribosomal proteins being one of the most highly transcribed. With microscope-based techniques that detect
mRNA and protein productions in the same single spore and mathematical models that screen various forms of
gene regulation, we are now uncovering signs of globally (genome-wide) coordinated transcription and
translation whose mechanisms we aim to elucidate in the next five years. Our ongoing work is also uncovering
dormant yeast spores secreting molecules that help each other survive, extend lifespans, and regulate gene
expression. We will elucidate the mechanisms of this "collective dormancy" and signs of aging in dormant yeast
spores. A comprehensive library of gene-deleted yeast strains will help us determine how each gene accelerates
or decelerates aging in dormant spores and its role in collective dormancy. Our work will advance the still-
primitive understanding of eukaryotic, microbial dormancy by establishing foundational knowledge on gene
regulation and aging in dormancy with quantitative approaches that have rarely been applied to these topics.
More broadly, we expect that our work will provide conceptual insights into quiescent cells i...

## Key facts

- **NIH application ID:** 10500669
- **Project number:** 1R35GM147508-01
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Hyun Youk
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $418,750
- **Award type:** 1
- **Project period:** 2022-08-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10500669

## Citation

> US National Institutes of Health, RePORTER application 10500669, Dynamics in Eukaryotic Dormancy: Gene Expression and Aging (1R35GM147508-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10500669. Licensed CC0.

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