# Non-transcriptional regulation of circadian physiology

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2024 · $497,223

## 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 govern rhythmic expression of genes involved in
diverse cellular processes. However, more recent studies have uncovered complementary non-
transcriptional mechanisms, including protein post-translational modifications (PTMs), that are
critical for maintaining 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 the timing and lipid content of metabolic
input from food intake 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 timing
of metabolic signals and clock-regulated lipid metabolism regulate S-palmitoylation rhythms and
how these rhythms are impacted by increased lipid content in food (Aim 1); to identify proteins
that exhibit daily rhythms in S-palmitoylation (Aim 2); and to determine if S-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:** 10823071
- **Project number:** 2R01DK124068-05A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** JOANNA Chungyen CHIU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $497,223
- **Award type:** 2
- **Project period:** 2019-09-11 → 2028-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10823071

## Citation

> US National Institutes of Health, RePORTER application 10823071, Non-transcriptional regulation of circadian physiology (2R01DK124068-05A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10823071. Licensed CC0.

---

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