# The Generation of Multi-Phasic Circadian Output

> **NIH NIH R35** · WASHINGTON UNIVERSITY · 2024 · $388,750

## Abstract

PROJECT SUMMARY/ ABSTRACT
 The purpose of an internal circadian clock is to generate a series of phases - time markers across the
day and night by which different aspects of physiology and behavior (e.g., sleep, hormone release,
temperature elevations) may be aligned to local time for optimal efficiency. We know a great deal about the
molecular mechanisms of the clock (the timekeeping system) and how it is sensitive to local time. We know
much less about circadian output, and specifically how the clock generates multiple phases across the entire
solar day. Such phases are used by other clock cells, and by non-clock bearing downstream cells and
circuits. Our laboratory studies circadian neurophysiology and the overall goal of this project is to understand
the generation and usage of different circadian phasic outputs. The work is performed in the model system
Drosophila. It builds on observations and a model we created from our past studies of the neural circuit in
the Drosophila brain that controls daily locomotor behavior. In the fly brain, ~150 dedicated circadian
pacemaker neurons direct daily rhythmic physiology and behavior. These 150 pacemakers are highly
synchronized: they all tell the same time. Our model features the cell-intrinsic molecular clock in all
pacemakers directing a morning phase of heightened neuronal activity. Yet, different subsets of pacemakers
are not all active in the morning, but at different and stereotyped times of the day and night. The diversity of
active periods (circadian phases) is generated primarily by cell interactions (especially neuropeptide
modulation) and together these activity periods represent the multi-phasic outputs of the pacemaker system.
Overall, this research program aims to extend and test this model by providing a cell- and molecular-level
understanding for how circadian phase information is transmitted beyond the pacemaker system and
received by downstream target circuits. Our work in Drosophila will likely inform our understanding of
circadian output in the mammalian brain, and will also be relevant more generally to the mechanisms of
neural circuit modulation by neuropeptides.

## Key facts

- **NIH application ID:** 10821487
- **Project number:** 5R35GM149192-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Paul H Taghert
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $388,750
- **Award type:** 5
- **Project period:** 2023-04-05 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10821487

## Citation

> US National Institutes of Health, RePORTER application 10821487, The Generation of Multi-Phasic Circadian Output (5R35GM149192-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10821487. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*