# Molecular Mechanisms Integrating Circadian Timing and Photic Signaling

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2020 · $345,625

## Abstract

Project Summary
Circadian clocks have evolved to appropriately align biological processes to the changing 24 h environment.
Genetic analyses of circadian locomotor activity rhythms in the fruit fly Drosophila have revealed transcriptional
feedback loops as the core organizing principle of circadian clocks. Yet the pace of these circadian feedback
loops is largely determined by protein phosphorylation and subsequent degradation, driving rhythmic
expression of clock components such as PERIOD (PER). In Drosophila, light is able to reset these oscillators
in part via degradation of the clock component TIMELESS (TIM). Remarkably, these clocks are highly
conserved among animals. Circadian clocks also enable the appropriate adaptation to seasonal changes in
day length or photoperiod. Yet while much is known about both core clock and photic input mechanisms, a
mechanistic understanding of how these two pathways collaborate to mediate responses light, including
changing photoperiod, is lacking in animals. Here a novel clock component has been discovered, the
phosphatase of regenerating liver-1 (PRL-1), that is also important for light mediated resetting and setting
behavioral phase under varying seasonal photoperiod. This research proposes to leverage the discovery of
PRL-1 to understand how the circadian clock integrates light information to drive appropriately timed behavior.
It will specifically address the neuronal basis of PRL-1 function including the role in specific photoreceptor
pathways, its function in autonomous and coupling neuronal oscillators, and the role of the light and clock
regulated clock component TIM in mediating PRL-1 effects. These studies exploit the discovery of a core clock
component with a novel role in photoperiod-dependent behavior. In addition, full advantage is taken of the
Drosophila system, including the conservation of the core clock machinery and clock neural network
architecture as well as extensive molecular genetic resources to examine gene function in the whole animal.
This research also leverages the ability to quantitatively examine molecular oscillations in FACS sorted and
intact neurons. This work could provide insights into how circadian clocks integrate environmental information
to yield timed behavior.

## Key facts

- **NIH application ID:** 9864115
- **Project number:** 5R01NS106955-03
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Ravi Allada
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $345,625
- **Award type:** 5
- **Project period:** 2018-05-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9864115

## Citation

> US National Institutes of Health, RePORTER application 9864115, Molecular Mechanisms Integrating Circadian Timing and Photic Signaling (5R01NS106955-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9864115. Licensed CC0.

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