# Investigating Circadian Post-Transcriptional Regulation.

> **NIH NIH R35** · RENSSELAER POLYTECHNIC INSTITUTE · 2020 · $382,252

## Abstract

Project Summary/Abstract:
 Circadian rhythms are highly conserved, roughly 24-hour, physiological cycles that adjust innumerable
actions, affecting everything from luminescence in bacteria to sleep in humans. Through the ideal programming
of behavior, it is believed that these rhythms enhance fitness by ensuring that many organismal functions are
optimally synchronized with the appropriate phase of the circadian day. Disruption of proper circadian timing
negatively impacts the human long-term medical outlook, making it critical to understand the mechanism
underlying circadian regulation over cellular physiology. Circadian rhythms are controlled via a highly-regulated
transcription-translation based negative feedback loop, or clock. The current paradigm for clock regulation over
cellular physiology is that transcriptional activity from the positive arm of the transcription–translation negative
feedback loop drives the expression of a host of gene promoters that modulate organismal behavior. However,
mounting evidence suggests that circadian regulation is imparted on cellular physiology beyond the level of
transcription and that the negative arm may play a role in this regulation. The long-term goal of our work is to
determine the extent of this post-transcriptional regulation on cellular physiology and to identify the mechanistic
underpinnings of circadian post-transcriptional regulation.
 As a mechanism for keeping time, transcription–translation negative feedback loops are highly conserved
and much of what is understood about the molecular clock comes from the investigation of model systems.
Therefore, we will exploit the simplicity and reproducibility of model systems to cost-effectively address our
hypotheses. To determine the extent of circadian post-transcriptional regulation, we will analyze the
transcriptome and proteome of murine macrophages over circadian time. As mice are a common model for the
human immune system, our study will garner insights into both the extent of circadian post-transcriptional
regulation as well as investigate clock regulation on the immune system. To tackle the mechanistic underpinnings
of post-transcriptional regulation, we will utilize Neurospora crassa, a bread mold whose ease of biochemical
and genetic manipulation is unparalleled in any other eukaryotic clock model system. We hypothesize that the
negative arm may control circadian output via transient protein-protein interactions, which are synchronized by
timed conformational changes that are enabled by the negative arm’s inherently flexible biochemical nature. We
will create a Conformational/Temporal Interactome (CTI) map of circadian negative arm proteins to validate our
hypothesis. Due to the conservation of clock architecture, the results of this work have the potential to define
several novel and unrecognized paradigms in clock regulation over cellular physiology.

## Key facts

- **NIH application ID:** 9983728
- **Project number:** 5R35GM128687-03
- **Recipient organization:** RENSSELAER POLYTECHNIC INSTITUTE
- **Principal Investigator:** Jennifer Marie Hurley
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $382,252
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9983728

## Citation

> US National Institutes of Health, RePORTER application 9983728, Investigating Circadian Post-Transcriptional Regulation. (5R35GM128687-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9983728. Licensed CC0.

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