PUBLICATION
Controlling the Circadian Clock with High Temporal Resolution through Photodosing
- Authors
- Kolarski, D., Sugiyama, A., Breton, G., Rakers, C., Ono, D., Schulte, A., Tama, F., Itami, K., Szymanski, W., Hirota, T., Feringa, B.L.
- ID
- ZDB-PUB-190912-10
- Date
- 2019
- Source
- Journal of the American Chemical Society 141(40): 15784-15791 (Journal)
- Registered Authors
- Breton, Ghislain
- Keywords
- none
- MeSH Terms
-
- Adenine/analogs & derivatives*
- Adenine/chemistry
- Adenine/pharmacology
- Animals
- Casein Kinase I/antagonists & inhibitors*
- Cell Line
- Circadian Clocks/drug effects*
- Circadian Clocks/radiation effects
- Circadian Rhythm/drug effects
- Circadian Rhythm/radiation effects
- Dose-Response Relationship, Drug
- Dose-Response Relationship, Radiation
- Humans
- Larva/drug effects
- Larva/enzymology
- Larva/radiation effects
- Light Signal Transduction
- Mice
- Molecular Docking Simulation
- Protein Kinase Inhibitors/chemistry
- Protein Kinase Inhibitors/pharmacology*
- Spleen/drug effects
- Spleen/enzymology
- Spleen/radiation effects
- Time Factors
- Ultraviolet Rays*
- Zebrafish/metabolism*
- PubMed
- 31509406 Full text @ J. Am. Chem. Soc.
Citation
Kolarski, D., Sugiyama, A., Breton, G., Rakers, C., Ono, D., Schulte, A., Tama, F., Itami, K., Szymanski, W., Hirota, T., Feringa, B.L. (2019) Controlling the Circadian Clock with High Temporal Resolution through Photodosing. Journal of the American Chemical Society. 141(40):15784-15791.
Abstract
Circadian clocks, biological timekeepers that are present in almost every cell of our body, are complex systems whose disruption is connected to various diseases. Controlling cellular clock function with high temporal resolution in an inducible manner would yield an innovative approach for the circadian rhythm regulation. In the present study, we present structure-guided incorporation of photoremovable protecting groups into a circadian clock modifier, longdaysin, which inhibits casein kinase I (CKI). Using photo-deprotection by UV or visible light (400 nm) as the external stimulus, we have achieved quantitative and light-inducible control over the CKI activity accompanied by an accurate regulation of circadian period in cultured human cells and mouse tissues, as well as in living zebrafish. This research paves the way for the application of photodosing in achieving precise temporal control over the biological timing and opens the door for chronophotopharmacology to deeper understand the circadian clock system.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping