# Neural and Molecular Mechanisms underlying Sleep and Metabolic Rhythms

> **NIH NIH R35** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $390,000

## Abstract

PROJECT SUMMARY/ABSTRACT
 Circadian rhythms are 24-hour oscillations in behavior and physiology that are conserved in
almost all forms of life on earth, enabling organisms to adapt to earth’s diurnal cycles.
Dysregulation of circadian clocks has been linked to many human pathologies, including
diabetes, obesity and neurodegenerative diseases. The long-term goal of my research is to
understand how circadian clocks are regulated and how their disruption leads to human
pathologies. In the next five years, I propose to investigate the neural and molecular basis of
circadian regulation in response to two external cues: temperature and food. Circadian rhythms
are self-sustained in constant conditions, but they have to be entrained/adjusted by external
cues such as light, temperature or food cycles daily to maintain a precise 24-hour period. Past
pioneering work has uncovered the major clock components and the mechanisms underlying
light entrainment and sleep-wake rhythms. However, the neural and molecular mechanisms by
which other external cues, temperature and rhythmic food intake, entrain the clock and the
related input and output mechanisms remain largely unexplored. I recently achieved a
breakthrough in understanding how circadian clock neurons process temperature information to
regulate sleep-wake rhythms. In this proposal, I seek to investigate the neural and molecular
mechanisms underlying temperature entrainment and food entrainment in Drosophila
melanogaster, a powerful model organism as it has a highly conserved clock similar to humans
along with superb genetic and behavioral tools. Specifically, I will first elucidate new
temperature input pathways and reveal the neural and molecular mechanisms that govern
sleep-wake rhythms under temperature cycles. In these efforts, I will use a multidisciplinary
approach combining novel instrumentation along with powerful genetic, molecular, behavioral,
and live imaging approaches. Next, to elucidate the mechanisms underlying food entrainment, I
will leverage novel high-resolution calorimetry and other tools that I recently developed that
makes it possible, for the first time, to both control the timing of food intake and monitor
metabolic rhythms from individual organisms. This work will uncover fundamental and important
new insights into circadian regulation which are expected to be highly evolutionarily conserved.
Further, this work can have several practical benefits as it may provide new opportunities for the
development of novel strategies to target clock machinery to treat diseases.

## Key facts

- **NIH application ID:** 10474557
- **Project number:** 5R35GM133737-04
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Swathi Yadlapalli
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $390,000
- **Award type:** 5
- **Project period:** 2019-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10474557

## Citation

> US National Institutes of Health, RePORTER application 10474557, Neural and Molecular Mechanisms underlying Sleep and Metabolic Rhythms (5R35GM133737-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10474557. Licensed CC0.

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