Circadian Clock Regulation in Skin

Summary

This project investigates how the circadian clock coordinates metabolism and cell cycle progression in epidermal stem cells to minimize DNA mutations and prevent skin aging, specifically examining the impact of time-restricted feeding.

What they want

The project aims to understand how the circadian clock coordinates oscillations of metabolism-generated ROS levels with the cell cycle and DNA repair machinery in epidermal stem cells to maximize their health and function. It hypothesizes that this regulation minimizes metabolism-generated ROS when most epidermal stem cells are undergoing DNA replication, the cell cycle stage most sensitive to oxidative DNA damage. The hypothesis predicts that daytime feeding-induced circadian misalignment in epidermal stem cells causes asynchrony between oxidative metabolism and the cell cycle, leading to increased ROS-induced DNA mutations, epidermal stem cell dysfunction, and skin aging.

Deliverables

Define the gene-regulatory mechanisms underlying time-restricted feeding modulation of the circadian clock and metabolism in epidermal stem cells.
Determine how time-restricted feeding modulates epidermal stem cell function and affects the rate of age-associated DNA mutations in epidermal stem cells.

Technical requirements

duplex DNA-sequencing
fluorescence lifetime imaging
single cell RNA-sequencing