Systems Level Understanding of Circadian Integration with Cell Physiology

Area of Science:

• Circadian Biology
• Systems Biology
• Genomics

Background:

• The mammalian circadian clock governs physiological and behavioral processes.
• Disruption of the circadian clock is linked to various disorders, including metabolic syndrome, neurological disorders, and cancer.
• The core clock mechanism involves a transcriptional negative feedback loop of clock genes, recently expanded into a complex network.

Purpose of the Study:

• To review genes and pathways that provide inputs to the circadian clock.
• To highlight the interplay between cellular physiology and the circadian clock.
• To identify areas for future research in understanding circadian regulation.

Main Methods:

• Literature review focusing on systems biology approaches.
• Analysis of genomic studies to understand clock network complexity.
• Identification and discussion of emerging input pathways to the circadian clock.

Main Results:

• Several input pathways, including AMP-activated protein kinase (AMPK), mTOR, SIRT1, HIF1α, NRF2, and NF-κB, extensively interact with the circadian clock.
• These pathways regulate core clock genes and proteins, demonstrating crosstalk between cell physiology and circadian timing.
• Precise molecular links and regulatory mechanisms underlying this crosstalk remain largely uncharacterized.

Conclusions:

• The circadian clock is intricately connected with cellular physiology through numerous input pathways.
• Further research using systems-based frameworks, genetic tools, and computational modeling is crucial to elucidate these complex regulatory mechanisms.
• Understanding these interactions may lead to strategies for enhancing circadian functions.