# Assessing Intertissue Communication in the Mammalian Circadian System

> **NIH NIH F31** · VANDERBILT UNIVERSITY · 2022 · $31,492

## Abstract

PROJECT SUMMARY/ABSTRACT
 Circadian rhythms are near 24-hour cycles in physiology that are fundamental to human health. Diseases
such as breast cancer and other metabolic disorders are associated with circadian rhythm disruptions because
of shiftwork, 24-hour lighting, chronic jet lag, and other factors of modern-day life. Circadian rhythms are created
by endogenous molecular oscillators, or clocks, that regulate transcriptional rhythms. Communication between
these clocks is integral to their function as a well-coordinated system. Despite their importance, circadian inter-
tissue communication mechanisms are poorly understood and properties that govern circadian coordination are
unknown. Yet, studies suggest that circulating endocrine factors, such as insulin and glucocorticoids, may play
a role in synchronization as they can phase shift core genes of the clock machinery. Thus, the hypothesis is that
endocrine pathways are sources of circadian inter-tissue communication and are affected by circadian
misalignment and disruption. Defining factors of inter-tissue communication between clocks and characterizing
temporal interactions in genome-scale data is critical to explain how tissues and organs orchestrate critical daily
programs such as metabolism.
 To investigate circadian function and gene regulation, studies use complex time-series designs to
manipulate clock genes and environmental conditions across one or multiple tissues. Yet, statistical and
analytical methods do not reliably quantify rhythmic effects (amplitude and phase) nor interaction effects with
conditions tested in such large-scale data. Yet, rhythmic properties such as amplitude and phase can fully
describe a gene’s rhythm and change to that rhythm (differential rhythmicity) as a result of perturbation in
complex experiments.
 The goal of this project is to identify factors of inter-tissue communication by addressing these statistical
challenges to circadian gene expression analysis. I will build a statistical framework to estimate effects for
amplitude and phase of genes in wild type experiments, as well as changes in amplitude and phase in
experiments with two or more conditions (differential rhythmicity). Properly quantifying these properties will
provide a detailed characterization of rhythmic features in genome-scale data. With these properties, I will
leverage publicly available circadian transcriptome data to analyze phase similarities in signaling pathways
between tissues and construct a map of potential inter-tissue signaling interactions across the day. This work
will identify components that define relationships between tissue clocks at the gene expression level. These
factors can be targeted as therapeutic agents for conditions caused by circadian disruption and dysregulation in
our everyday life.

## Key facts

- **NIH application ID:** 10468657
- **Project number:** 5F31GM143909-02
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Dora Obodo
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $31,492
- **Award type:** 5
- **Project period:** 2021-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10468657

## Citation

> US National Institutes of Health, RePORTER application 10468657, Assessing Intertissue Communication in the Mammalian Circadian System (5F31GM143909-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10468657. Licensed CC0.

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