# Exploring the molecular mechanisms of body temperature rhythms through a Drosophila model system

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2020 · $200,000

## Abstract

PROJECT SUMMARY: The specific goal of this project is to identify novel molecular and neural mechanisms of
circadian rhythm, focusing on the regulatory mechanisms that underlie body temperature rhythm (BTR). In
humans, BTR is typified by temperature increases during wakefulness and decreases during sleep, and is a
robust output of the circadian clock. Furthermore, BTR maintains homeostasis, including the homeostasis of
metabolism and sleep, and entrains peripheral clocks in mammals. Importantly, BTR is regulated in a manner
distinct from locomotor activity rhythms; therefore, the neural mechanisms and circuits of BTR are separate from
those of locomotor activity rhythms.
 In this R21 exploratory grant, we will focus on BTR-specific neural mechanisms and circuits; to do so, we
will use Drosophila temperature preference behavior as an innovative and robust form of experimental output.
We previously demonstrated that Drosophila exhibit a temperature preference rhythm (TPR), in which the
preferred temperature increases during the day and decreases at the transition from day to night. Unlike
mammals, which generate internal heat to regulate BTR, Drosophila rely on behavioral strategies to regulate
their daily body temperature changes. Therefore, Drosophila TPR produces BTR through the physical selection
of a preferred environmental temperature.
 Through studies of Drosophila TPR behavior, we recently identified that DH31R, a Drosophila G-protein-
coupled receptor in clock neurons, mediates TPR. Furthermore, we determined that the closest homolog of
DH31R in mice, calcitonin receptor (CALCR), is expressed in the shell suprachiasmatic nucleus (SCN) to
mediate BTR. Importantly, neither DH31R in flies nor CALCR in mice is involved in locomotor activity rhythmicity.
These findings provided the first molecular evidence that BTR is regulated apart from locomotor activity rhythms.
Our data suggest that fly TPR is likely regulated by mechanisms similar to that of mammalian BTR and vice
versa; therefore, we expect that specific neural and molecular mechanisms in control of fly TPR are conserved
in mammals. Two specific aims are proposed: In Aim 1, we will Identify gene profiles that are selectively and
highly expressed in DN2s. In Aim 2, we will determine candidate genes which play important role in TPR.
 Upon completion of the proposed work, our expectation is to have identified genes that are important to
regulate TPR, including dynamic changes to the TPR neural circuitry. Further, our examination of Drosophila
TPR behavior will comprise an innovative, robust, and sophisticated approach to elucidate the neural
mechanisms that regulate BTR. The outcome of this study is expected to establish a solid foundation to
understand the mechanisms of BTR in mammals, lending important and actionable insights into the treatment of
circadian clock diseases, sleep problems, and the health of night-shift workers.

## Key facts

- **NIH application ID:** 10440755
- **Project number:** 7R21NS112890-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Fumika Hamada
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $200,000
- **Award type:** 7
- **Project period:** 2020-04-01 → 2022-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10440755

## Citation

> US National Institutes of Health, RePORTER application 10440755, Exploring the molecular mechanisms of body temperature rhythms through a Drosophila model system (7R21NS112890-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10440755. Licensed CC0.

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