Molecular Underpinnings of the Mammalian Circadian Clock
Most organisms from bacteria to humans exhibit endogenous 24-hours (circadian) rhythms . Best exemplified by the sleep/wake cycle, these rhythms are remarkably widespread and include in humans hormonal, metabolic, physiological and behavioral oscillations. These rhythms have a remarkable adaptive value as they enable most biological functions to be rhythmic and set to perform optimally at the most appropriate time of the day.
Circadian rhythms are generated by “molecular clocks”, which consist of “clock genes” interacting in transcriptional feedback loops to drive the rhythmic expression of a large number of genes, i.e. ~15% of the transcriptome in any tissues. This wide impact of clock genes in regulating gene expression is underscored by the surprisingly large number of pathologies developed by clock-deficient mice. In addition to being arrhythmic, they indeed develop pathologies as diverse as mania-like behaviors, learning and memory defects, depression, drug addiction, insomnia, metabolic diseases, arthropathy, hematopoiesis defects and cancers.
Research in the Menet lab aims at characterizing how circadian clocks and clock genes regulate gene expression to provide insights into how and why clock dysfuntion leads to a wide spectra of pathologies. To this end, we are using a wide-range of molecular, biochemical and physiological techniques to investigate the circadian clock function at the genome-wide level. We are currently extending some of our recent results and focus on 1) how clock genes rhythmically regulate chromatin environment and 2) the mechanisms involved in rhythmic transcriptional and post-transcriptional regulation of gene expression.
October 2019: Ben presented at the TAMU Student/Postdoc Research Conference (SPRC) 2019 meeting. Great talk on his new project!
September 2019: Josh successfully defended her Ph.D. Congrats Josh!
January 2019: Aishwarya joins the lab!
Lugena AB, Zhang Y, Menet JS, Merlin C. (2019) Genome-wide discovery of the daily transcriptome, DNA regulatory elements and transcription factor occupancy in the monarch butterfly brain. PLoS Genet. 15(7):e1008265.
Greenwell BJ, Trott AJ, Beytebiere JR, Pao S, Bosley A, Beach E, Finegan P, Hernandez C, Menet JS. (2019) Rhythmic Food Intake Drives Rhythmic Gene Expression More Potently than the Hepatic Circadian Clock in Mice. Cell Rep 27(3):649-657.e5.