# Genetic mechanisms specifying astrocyte functional diversity and their role in sleep

> **NIH NIH K99** · JOHNS HOPKINS UNIVERSITY · 2021 · $87,728

## Abstract

Project Summary
Astrocytes are evolutionarily conserved and constitute a substantial proportion of the cells in the brain, yet our
understanding of their identities and functions is far less comprehensive than for neurons. Astrocytes are
thought to be important for regulating the formation and function of neuronal circuits, playing multiple roles in
neurotransmitter reuptake, ionic buffering, metabolic support, and plasticity. Evidence from both mammals and
Drosophila has also indicated that astrocytes are diverse in both function and morphology. However, the
underlying genetic mechanisms and the functional importance of this diversity remain unclear. The focus of this
grant is to characterize the functional and molecular diversity of astrocytes in the adult Drosophila central brain
and their role in sleep, a conserved innate behavior. In Aim 1, I will systematically investigate genes regulating
astrocyte heterogeneity, specifically their regional specification and morphology. I will also use single cell RNA
sequencing to identify differentially expressed genes within astrocytes and visualize the spatiotemporal pattern
of gene expression in astrocytes in the central brain. Completion of this aim will lay the foundation for a
comprehensive cataloging of astrocyte identity and morphology in Drosophila. In Aim 2, I will study the role of
local astrocyte-neuron interactions in regulating sleep and arousal using in vivo calcium imaging,
electrophysiology and behavioral assays. In Aim 3 during the R00 phase, I will generate tools to make stable
intersectional reagents for targeting of specific astrocyte populations that will be broadly useful for labeling and
functional manipulation. I will use these tools to further dissect the diverse roles of astrocytes in regulating
sleep behavior. The research arising from this proposal will greatly expand our knowledge of astrocyte biology,
by 1) identifying the genes and molecules responsible for astrocyte function and diversity, 2) elucidating their
interactions with neuronal circuits and how they regulate behavior, and 3) development tools to target and
manipulate this important cell type. Importantly, the training plan, including coursework, professional
development, and mentorship from experts in neurobiology, astrocytes, and genetic tool-building, will prepare
me for a future career as an independent academic neuroscientist.

## Key facts

- **NIH application ID:** 10222798
- **Project number:** 5K99NS117654-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Margaret Ho
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $87,728
- **Award type:** 5
- **Project period:** 2020-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10222798

## Citation

> US National Institutes of Health, RePORTER application 10222798, Genetic mechanisms specifying astrocyte functional diversity and their role in sleep (5K99NS117654-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10222798. Licensed CC0.

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