# Reconstructing the temporal landscape of gene regulation in aging

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2020 · $378,976

## Abstract

PROJECT SUMMARY / ABSTRACT
The circadian rhythm orchestrates a vast repertoire of biochemical, physiological, and behavioral processes with
a 24-hour period. A clock circuit, driven by the oscillatory activation and repression of a set of core clock genes,
is present in every cell and regulates the expression of nearly half the genome across all tissues. Abundant epi-
demiological evidence links circadian regulation to human health. In particular, sleep and circadian disruption is
associated with neurodegeneration, where it is thought to be both a consequence and a risk factor for Alzheimer's
disease (AD). As the most common form of dementia in the elderly, AD is rapidly becoming a public health cri-
sis, affecting an estimated 5.5M people in the United States (24M world-wide) and is expected to double over the
next 20 years. Addressing this crisis requires a deep understanding of disease mechanisms and the identification
of diagnostic/therapeutic targets. A wealth of existing transcriptomic data, coupled with the development of
sophisticated computational tools for temporal reconstruction and analysis, provide an exciting opportunity to
identify dysregulation in oscillatory patterns of gene expression associated with aging and AD.
 We propose to develop novel computational strategies to decipher the oscillatory patterns of gene expression
using existing untimed transcriptomic datasets; and to apply them to existing data from studies of AD to identify
dysregulation in the oscillatory patterns associated with AD. Our methods address a number of analytical chal-
lenges, including the need to reconstruct temporal information from untimed samples; ensuring generalizability
and accuracy across different transcriptomic profiling technologies; addressing the fact that untimed samples
may not span the full day; and identifying changes in complex, non-sinusoidal rhythms. Together, these studies
will reveal oscillatory patterns of gene expression associated with aging and Alzheimers disease, and will provide
innovative new methods for the circadian analysis of untimed data that can be applied to other phenotypes.

## Key facts

- **NIH application ID:** 10046159
- **Project number:** 1R01AG068579-01
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Rosemary Braun
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $378,976
- **Award type:** 1
- **Project period:** 2020-09-15 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10046159

## Citation

> US National Institutes of Health, RePORTER application 10046159, Reconstructing the temporal landscape of gene regulation in aging (1R01AG068579-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10046159. Licensed CC0.

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