# Non-transcriptional regulation of circadian physiology

> **NIH NIH R56** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2023 · $137,040

## Abstract

PROJECT SUMMARY
Robust daily biological rhythms are key hallmarks of animal healthspan and are strongly
regulated by circadian clocks. These cell-autonomous molecular timers enable animals to adapt
to predictable daily changes in their environment. Clock-controlled outputs are all-encompassing
and clock disruption is associated with a wide range of pathologies and chronic diseases. In the
natural world, environmental signals, e.g. light and temperature, enable animal circadian clocks
to control timing of food intake. Nutrient influx can therefore provide metabolic signals to reinforce
environmental signals, promoting synchrony in cellular physiology to balance metabolism and
energy use. Efforts to understand the underpinnings of circadian clocks and their control over
daily biological rhythms have long focused on regulation at the transcriptional level, as core
oscillator proteins are transcription factors that collaborate to govern rhythmic expression of genes
involved in diverse cellular processes. More recent studies have uncovered complementary non-
transcriptional mechanisms, including protein post-translational modifications (PTMs), that are
critical for robust daily rhythms. The overall goal of this project is to advance our understanding
of the role of nutrient-dependent PTMs in mediating metabolic regulation of time-of-day-specific
protein functions to orchestrate daily biological rhythms. We will use the diurnal Drosophila model
to test the central hypothesis that metabolic signals from clock-controlled feeding activity and
cellular metabolism regulate rhythmic S-palmitoylation of cellular proteins, and S-palmitoylation
is necessary for maintenance of robust daily biological rhythms. S-palmitoylation is the only
reversible lipid PTM; it is the attachment of palmitate, a saturated fatty acid, to cysteines. S-
palmitoylation targets a wide range of proteins from transcription factors to membrane receptors,
and is known to alter their stability, activity, localization, and protein-protein interactions. The
specific aims of this project are to investigate the mechanisms by which clock-dependent
metabolic signals regulate S-palmitoylation rhythms and how these rhythms are impacted by
nutritional stress (Aim 1); to identify proteins that exhibit daily rhythms in S-palmitoylation (Aim 2);
and to determine if palmitoylation regulates daily biology rhythms (Aim 3). This project will
advance our long-term goal to integrate post-translational regulatory pathways and obtain a
comprehensive understanding of how daily biological rhythms are regulated by diet, nutrition, and
timing of metabolic input. This project will have broad significance as misregulation in S-
palmitoylation has been linked to a plethora of human diseases including cancer, metabolic,
neurological, and immunological disorders.

## Key facts

- **NIH application ID:** 10835328
- **Project number:** 2R56DK124068-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** JOANNA Chungyen CHIU
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $137,040
- **Award type:** 2
- **Project period:** 2019-09-11 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10835328

## Citation

> US National Institutes of Health, RePORTER application 10835328, Non-transcriptional regulation of circadian physiology (2R56DK124068-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10835328. Licensed CC0.

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