# Sex differences in circadian output signaling

> **NIH GM R35** · RUTGERS, THE STATE UNIV OF N.J. · 2026 · $392,500

## Abstract

PROJECT SUMMARY/ABSTRACT
Circadian rhythms are the backing track to the symphony of life. Circadian rhythms not only allow organisms to
coordinate their behavior and physiology with daily and seasonal changes but also temporally coordinate
internal processes across organ systems. However, genetic, molecular, circuit, metabolic, and behavioral
studies of chronobiology have been conducted primarily in male animals. Although the overall architecture of
circadian systems is conserved across phylogeny and between sexes, circadian systems are not identical
between sexes. This proposal exploits the Drosophila melanogaster genetic model to identify sex
differences in circadian output signaling from the brain clock to peripheral metabolic tissues. We have
identified two major knowledge gaps: (1) Sex differences in circuitry and signaling from the brain clock to clock
output regions that communicate time of day to peripheral tissues; and (2) Sex differences in peripheral
responses to circadian entrainment at baseline and when exposed to clock desynchronizing stressors. Our
published and preliminary data has identified sex differences in the role of specific clock output neuropeptides
in regulating circadian behavior and shown that age and high-fat diet have separable effects on dampening
circadian rhythms of locomotor behavior and peripheral gene expression. In Project 1, we will use in vivo and
in silico circuit mapping techniques to identify how sex-specific circuitry interacts with circadian clock outputs,
identify sex specific transcriptional programs that alter morphology, cell number, connections, and physiology
of clock output neurons, and use CRISPR knockout screening to identify specific signaling molecules and
cognate receptors that contribute to sexually dimorphic circadian output signaling. In Project 2, we will use a
novel long-term circadian luminescence imaging approach to identify how circadian gene transcription rhythms
break down in peripheral tissues in res

## Key facts

- **NIH application ID:** 11321240
- **Project number:** 5R35GM155111-03
- **Recipient organization:** RUTGERS, THE STATE UNIV OF N.J.
- **Principal Investigator:** Annika Fitzpatrick Barber
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** GM
- **Fiscal year:** 2026
- **Award amount:** $392,500
- **Award type:** 5
- **Project period:** 2024-07-05T00:00:00 → 2029-04-30T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11321240

## Citation

> US National Institutes of Health, RePORTER application 11321240, Sex differences in circadian output signaling (5R35GM155111-03). Retrieved via AI Analytics 2026-09-09 from https://api.ai-analytics.org/grant/nih/11321240. Licensed CC0.

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