# The Molecular and Cellular Basis of the Sleep Homeostat

> **NIH NIH R35** · NORTHWESTERN UNIVERSITY · 2023 · $1

## Abstract

Project Summary
Understanding why we sleep remains one of the most enduring mysteries in science. Nearly every
organism examined, even jellyfish that lack a centralized nervous system, exhibits a restorative
sleep-like state. While asleep, we cannot eat, mate, defend ourselves from predators or care for
our young. Inadequate sleep contributes to brain disease such as Alzheimer's and depression,
and even diseases outside of the brain, such as diabetes and obesity. Sleep is homeostatically
regulated, i.e., sleep is driven by the duration and intensity of prior waking experience. However,
the mechanistic basis of the sleep homeostat remains unclear. How does wakefulness tax the
brain? How does the homeostat sense those effects? How does the homeostat trigger sleep?
How does sleep restore the brain? Almost uniquely among brain functions, sleep requires the
coordinated activity of widespread brain regions. We aim to reveal the molecular and circuit basis
of the sleep homeostat using a simple animal model Drosophila. We will apply innovative
genetically targeted transcriptomic and proteomic approaches such as single-cell RNA
sequencing and enzymatic proximity labeling in the compact Drosophila brain to provide insights
into sleep-dependent genomic and proteomic changes at single gene, single protein, and single
cell resolution. We will then exploit the power of Drosophila genetics to assess the functional
impact of sleep/wake dependent neurons and genes by examining effects on sleep including
sleep-dependent functions including memory consolidation and lifespan. Based on our discovery
that neural mechanisms controlling the circadian regulation of sleep are widely conserved, we
predict that core homeostatic mechanisms will similarly be widely conserved. The integration of
these experimental approaches will produce mechanistic insights that link gene to neuron to
behavior and should reveal transformative insights into the components, logic, and function of the
sleep homeostat.

## Key facts

- **NIH application ID:** 10665203
- **Project number:** 1R35NS132223-01
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Ravi Allada
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $1
- **Award type:** 1
- **Project period:** 2023-05-17 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10665203

## Citation

> US National Institutes of Health, RePORTER application 10665203, The Molecular and Cellular Basis of the Sleep Homeostat (1R35NS132223-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10665203. Licensed CC0.

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