Interplay between Circadian and Redox Oscillations in Eukaryotes
Event details
| Date | 09.06.2016 |
| Hour | 11:00 |
| Speaker | Guillaume Rey, Ph.D., University of Cambridge, Cambridge (UK) |
| Location | |
| Category | Conferences - Seminars |
BIOENGINEERING SEMINAR
Abstract:
The circadian clock is a ubiquitous timekeeping system that organizes the behaviour and physiology of organisms over the day and night. Current models rely on transcriptional networks that coordinate circadian gene expression of thousands of transcripts. However, recent studies have uncovered phylogenetically conserved redox rhythms that can occur independently of transcriptional cycles. Here we identify the pentose phosphate pathway (PPP), a critical source of the redox cofactor NADPH, as an important regulator of redox and transcriptional oscillations. Our results show that genetic and pharmacological inhibition of the PPP prolongs the period of circadian rhythms in human cells, mouse tissues and in fruit flies. These metabolic manipulations also cause a remodelling of circadian gene expression programmes that involves the circadian transcription factors BMAL1/CLOCK, and the redox-sensitive histone acetyltransferase p300. Thus, the PPP regulates circadian rhythms via NADPH metabolism, suggesting a pivotal role for NADPH availability in circadian timekeeping.
Bio:
Mar 2012–present Research Associate, Department of Clinical Biochemistry, University of Cambridge, Cambridge (UK)
Jul 2007–Sep 2011 PhD Student, School of Life Sciences, EPFL, Lausanne (CH)
Abstract:
The circadian clock is a ubiquitous timekeeping system that organizes the behaviour and physiology of organisms over the day and night. Current models rely on transcriptional networks that coordinate circadian gene expression of thousands of transcripts. However, recent studies have uncovered phylogenetically conserved redox rhythms that can occur independently of transcriptional cycles. Here we identify the pentose phosphate pathway (PPP), a critical source of the redox cofactor NADPH, as an important regulator of redox and transcriptional oscillations. Our results show that genetic and pharmacological inhibition of the PPP prolongs the period of circadian rhythms in human cells, mouse tissues and in fruit flies. These metabolic manipulations also cause a remodelling of circadian gene expression programmes that involves the circadian transcription factors BMAL1/CLOCK, and the redox-sensitive histone acetyltransferase p300. Thus, the PPP regulates circadian rhythms via NADPH metabolism, suggesting a pivotal role for NADPH availability in circadian timekeeping.
Bio:
Mar 2012–present Research Associate, Department of Clinical Biochemistry, University of Cambridge, Cambridge (UK)
Jul 2007–Sep 2011 PhD Student, School of Life Sciences, EPFL, Lausanne (CH)
Practical information
- Informed public
- Free