# Understanding the effects of sleep deprivation on the gut's cellular homeostatic process

> **NIH NIH F32** · HARVARD MEDICAL SCHOOL · 2024 · $76,756

## Abstract

Project Summary
Individuals that suffer from chronic sleep disturbances are at high risk of developing intestinal dysfunction, which can
promote acute cardiovascular and cardiometabolic diseases. My lab recently discovered that sleep and the gut have a
bidirectional relationship. They found that the gut is specifically and critically injured during chronic sleep loss: sleep
suppression causes the accumulation of reactive oxygen species (ROS) in this organ, which in turn causes oxidative stress
and premature death of animals. The lab also uncovered a gut-to-brain peptidergic signaling pathway that regulates sleep
depth. It is critical to determine how low sleep amount and poor sleep quality negatively impact the gut's physiology and
function. I will use fruit flies as a model system to study the fundamental molecular, cellular, and functional relationship
between sleep and the gut. My study will test the hypothesis that sleep loss results in an altered gut cellular composition
that promotes increased sleep depth during recovery from sleep loss. The first aim of the proposal will focus on determining
changes to gut cell composition in chronically sleep-deprived flies. I propose that sleep loss promotes intestinal stem cell
proliferation and biases daughter cells toward enteroendocrine cell fate (gut sensory and secretory cells). I will combine
immunofluorescence and fluorescent reporters to determine changes in intestinal stem cell proliferation and enteroendocrine
cell fate determination. The second aim will examine sleep quality and lifespan in flies recovering from chronic sleep loss.
I propose that changes in the gut cellular composition resulting from chronic sleep loss promote deeper sleep in flies
recovering from sleep loss as a way to compensate for insufficient sleep. I will quantify the depth of sleep in chronically
sleep-deprived flies throughout their lifespan and perform functional experiments to assess if peptides secreted by the
enteroendocrine cells are responsible for increasing the depth of sleep during recovery. I will also functionally determine
the contribution of these enteroendocrine cell-secreted peptides to the longevity of flies recovering from chronic sleep loss.
Defining how cellular changes in the gut can impact the function of this organ and its role in regulating sleep will be
fundamental for understanding the bidirectional sleep-gut relationship. More generally, this work will contribute to
understanding how sleep problems negatively affect health and suggest solutions for how many of the problems can be
reversed.

## Key facts

- **NIH application ID:** 10929341
- **Project number:** 5F32HL168844-02
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Alejandra Sofia Laureano Ruiz
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $76,756
- **Award type:** 5
- **Project period:** 2023-04-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10929341

## Citation

> US National Institutes of Health, RePORTER application 10929341, Understanding the effects of sleep deprivation on the gut's cellular homeostatic process (5F32HL168844-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10929341. Licensed CC0.

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