# Development and Function of Sleep Circuits - Extramural Research Programs in the Neurosciences and Neurological Disorders

> **NIH NIH R01** · RUTGERS, THE STATE UNIV OF N.J. · 2022 · $398,251

## Abstract

We have little current understanding of the genetic and molecular mechanisms that link brain
development and the proper regulation of sleep throughout life. Understanding these mechanisms is a
longstanding challenge in sleep biology with great clinical relevance. Neurodevelopmental disorders including
autism are prevalent and closely associated with sleep disturbances, but the underlying genetic and
neuroanatomical mechanisms remain obscure. Our studies use the powerful Drosophila model system to
characterize a conserved genetic pathway whose activity is required during neuronal development for the
sleep regulation in adulthood. This pathway is composed of Insomniac (Inc), the Cullin-3 (Cul3) ubiquitin
ligase, and their targets. Reduced activity of this pathway in the developing brain severely curtails the duration
and consolidation of sleep in adulthood. Our findings suggest that this pathway has two distinct developmental
functions that influence the structure and function of the mushroom body, a sleep regulatory center in the fly
brain. In Aim 1 we will determine whether inc acts in neuroblasts to control the proliferation and number of
sleep-regulatory neurons. We will also validate Inc substrates, including a target that may link Inc to
asymmetric neuroblast division. In Aim 2, we will determine whether inc acts post-mitotically to regulate the
structure and anatomy of sleep-regulatory neurons. In Aim 3, we will determine how inc affects the function of
sleep-regulatory circuits. Because all of the genes under study are conserved and expressed in the
mammalian brain, our studies may provide insight into mechanisms underlying normal sleep, sleep
dysfunction, and various neurological disorders.

## Key facts

- **NIH application ID:** 10574347
- **Project number:** 7R01NS112844-03
- **Recipient organization:** RUTGERS, THE STATE UNIV OF N.J.
- **Principal Investigator:** Nicholas Stavropoulos
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $398,251
- **Award type:** 7
- **Project period:** 2020-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10574347

## Citation

> US National Institutes of Health, RePORTER application 10574347, Development and Function of Sleep Circuits - Extramural Research Programs in the Neurosciences and Neurological Disorders (7R01NS112844-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10574347. Licensed CC0.

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