Redox Potential as an Interface between Sleep homeostasis and Circadian Rhythms

Objective

Sleep is regulated by a homeostatic process that is activated by and counters the effect of sleep loss and a circadian process that determines the time-of-day sleep preferably occurs. The fine-tuned interaction between the two permits us to stay awake throughout the day and to remain asleep at night. Although these two processes are widely thought to operate independently, recent observations suggest that, at a molecular level, both processes use the same circadian transcription factors. Moreover, in vitro assays demonstrated that the activity of the two main circadian clock genes, Clock and Npas2, depend on intracellular redox potential, suggesting that, like sleep, circadian rhythms are intricately associated with cellular metabolism. The aim of this proposal is to analyze, in vivo, the relationship between sleep, circadian rhythms and cellular energy charge in order to better understand the cellular mechanisms that determine our day-time performance and sleep quality. By using redox-sensitive green fluorescent proteins (roGFPs), we will track redox changes within individual fibroblasts in which robust circadian rhythms can be induced, to establish that circadian rhythmicity is accompanied by changes in redox potential. Subsequently, the sleep-wake dependent and circadian contributions to changes in intracellular redox potential will be quantified in transgenic mice constitutively expressing roGFPs. Because clock-gene expression in the brain seems highly compartmentalized, we will follow changes in redox potential using optic-fibers aimed at the SCN (suprachiasmatic nucleus), the master circadian pacemaker, and in the cortex in freely behaving mice. Finally, we will establish how intracellular redox changes in SCN and cortex relate to the expression of the CLOCK and NPAS2 target gene period (per) 2, by studying per2-luciferase knock-in mice. These mice allow us to investigate how circadian rhythms in per2 expression in the periphery are coordinated by the SCN.

Fields of science (EuroSciVoc)

CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.

• natural sciences biological sciences biochemistry biomolecules proteins
• medical and health sciences basic medicine physiology homeostasis

Keywords

Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)

• Bioluminescent/Fluorescent Genetic probes
• Circadian rhythms
• Excitation spectra
• Imaging for whole living transgenic mice
• Metabolism
• Neurophysiology
• Redox potential
• Sleep homeostasis

Programme(s)

Multi-annual funding programmes that define the EU’s priorities for research and innovation.

• FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)

Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

• PEOPLE-2007-2-1.IEF - Marie Curie Action: "Intra-European Fellowships for Career Development"

Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

FP7-PEOPLE-2007-2-1-IEF
See other projects for this call

Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

MC-IEF - Intra-European Fellowships (IEF)

Coordinator