# Mechanism of Sleep Regulation by SIK3

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2024 · $398,877

## Abstract

Project Summary
Sleep and metabolic disorders are often comorbid, but how they interact is poorly understood. The salt
inducible kinase SIK3 was identified (first in C. elegans and 8 years later in flies and mice) as a sleep drive
regulator. Our findings suggest that SIKs connect sleep and metabolic regulation. In the prior funding cycle, we
demonstrated hierarchical somatic/neural interactions regulating both sleep and energy homeostasis. We have
shown that the sleep and energy-regulating roles of KIN-29/SIK occur by inhibiting the class 2 histone
deacetylase HDA-4 (HDAC4) in 12 pairs of glutamatergic neurons. Illuminating the mechanism by which KIN-
29 signals in glutamatergic neurons during high sleep drive will be the goal of aim 1. We will study the role of
CREB and CREB-regulated transcription coactivator 1 (CRTC1) in glutamatergic neurons. In aim 2, we will
test the hypothesis that reactive oxygen species promote sleep. In aim 3 we will test the hypothesis that NAD+
precursors promote sleep and are reduced in kin-29 mutants. Finally, in aim 4, we will identify genes whose
expression is regulated by the KIN-29--|HDA-4 signaling module. Such genes will be candidates for mediating
sleep-promoting signaling by glutamatergic neurons. At the completion of these aims, we will have an
improved understanding of the genetic and metabolic regulation of sleep. Data collected in aim 4 will motivate
additional genetic hypotheses that will be tested in future research.

## Key facts

- **NIH application ID:** 10801089
- **Project number:** 2R01NS107969-06
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** David Menassah Raizen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $398,877
- **Award type:** 2
- **Project period:** 2019-04-01 → 2029-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10801089

## Citation

> US National Institutes of Health, RePORTER application 10801089, Mechanism of Sleep Regulation by SIK3 (2R01NS107969-06). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10801089. Licensed CC0.

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