# Interdisciplinary Studies of Sleep and Circadian Rhythms

> **NIH NIH R37** · ROCKEFELLER UNIVERSITY · 2020 · $593,176

## Abstract

Project Summary/Abstract
Our genetic screens in Drosophila previously identified several mutations with strong effects on
patterns of sleep. Recently we found that three of these genes, insomniac, cullin3 and nedd8, are
expressed in the blood-brain-barrier-forming subperineurial glia of the fly, and that the
morphological and biophysical properties of the barrier are altered in inc, cullin3, and nedd8
mutants. In our proposed studies we will test the effects of classical barrier mutants on sleep,
evaluate barrier function across the entire range of available sleep mutants and in aged vs young
flies, and explore evidence for regulatory interactions among sleep and classical barrier-regulating
genes. Most Drosophila sleep mutants severely reduce longevity. We will determine whether
mutations that increase longevity also improve barrier function and sleep duration in sleep
mutants. In a second branch of our proposed research we will examine the role of circadian clock
genes in commonly encountered disorders of human sleep. We recently discovered a mutation of
the circadian clock gene CRY1 that is associated with a form of delayed sleep phase disorder
(DSPD) that affects ~1 in 100 individuals worldwide. The results of our study suggest a novel
approach for exploring the heritability of similarly common sleep disorders: Predictive algorithms
will be applied to several large human exome databases to select candidate circadian variants for
cellular phenotyping. Prevalent alleles that are associated with altered circadian rhythmicity in cell
culture assays also will be studied by behavioral phenotyping of carrier subjects identified by
collaborators at Bilkent University in Ankara, Turkey. Disordered sleep is often accompanied by
chronic diseases including diabetes, obesity, or certain mood and anxiety disorders. Although
causality in such instances has been difficult to establish by traditional approaches, we will employ
deep physiological and behavioral phenotyping of individuals sharing specific genetic variations
affecting sleep in tests for linkage to specific co-morbidities. These studies may significantly enrich
our understanding of biological pathways regulated by circadian clocks in humans as well as
fundamental disease etiologies.

## Key facts

- **NIH application ID:** 9842015
- **Project number:** 5R37NS053087-13
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **Principal Investigator:** Michael Warren Young
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $593,176
- **Award type:** 5
- **Project period:** 2006-02-03 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9842015

## Citation

> US National Institutes of Health, RePORTER application 9842015, Interdisciplinary Studies of Sleep and Circadian Rhythms (5R37NS053087-13). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9842015. Licensed CC0.

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