François Rouyer Team

Molecular Genetics of Circadian Rhythms

In brief

Our research aims at understanding how the brain controls sleep-wake rhythms. Sleep-wake rhythms are controlled by a brain circadian clock that is synchronized with day-night cycles by environmental cues, such as light and temperature. We use neurogenetics approaches in Drosophila to understand how a multi-oscillators brain clock is organized at the molecular and cellular levels as well as at the scale of neuronal networks, how the brain translates circadian information into sleep-wake rhythms, and how sensory signals are integrated to entrain the clock neuronal network and adapt the behavior to the environment.

Our research

Our projects address the following questions.
• How does the molecular machinery that is running in the clock cells generate a 24h (circadian) oscillation: we analyze the function and regulation (transcriptional, post-transcriptional and post-translational controls) of key clock genes (Clock, period, timeless) and search for new clock components.
• How natural genetic variation shapes individual sleep-wake rhythm phenotypes in various environmental conditions: we analyze the behavior of fully sequenced isogenic lines derived from individuals caught in the wild to identify new variants of clock and light-input components.
• What is the neuronal basis of the brain circadian clock: we study the behavioral contribution of the different neuronal oscillators and their communication through neuropeptides (PDF and ITP) or other neurotransmitters to understand the rules operating in the clock neuronal network.
• How do light changes synchronize the brain clock neuronal network with day-night cycles and modify its properties to adapt the behavior to the daily and seasonally changing environment: we characterize the neuronal and molecular pathways (photoreception through the visual system and cryptochrome) that transmit light signals to the clock neurons and their molecular oscillator.
• How is the circadian information that is generated by the clock neurons translated into sleep-wake behavior: we search for clock neurons' targets through anatomical and functional analysis and study sleep control features encoded by the clock neurons.

Selected Publications

> Grima, B., Papin, C., Martin, B., Chélot, E., Ponien, P., Jacquet, E., and Rouyer, F. (2019). PERIOD-controlled deadenylation of the timeless transcript in the Drosophila circadian clock. Proc Natl Acad Sci U S A 116, 5721-5726. Doi: 10.1073/pnas.1814418116

> Alejevski, F., Saint-Charles, A., Michard-Vanhée, C., Martin, B., Galant, S., Vasiliauskas, D., and Rouyer, F. (2019). The HisCl1 histamine receptor acts in photoreceptors to synchronize Drosophila behavioral rhythms with light-dark cycles. Nat Commun 10, 252. Doi: 10.1038/s41467-018-08116-7

> Szabó, Á., Papin, C., Cornu, D., Chélot, E., Lipinszki, Z., Udvardy, A., Redeker, V., Mayor, U., and Rouyer, F. (2018). Ubiquitylation Dynamics of the Clock Cell Proteome and TIMELESS during a Circadian Cycle. Cell Rep 23, 2273-2282. Doi: 10.1016/j.celrep.2018.04.064

> Chatterjee, A., Lamaze, A., De, J., Mena, W., Chélot, E., Martin, B., Hardin, P., Kadener, S., Emery, P., and Rouyer, F. (2018). Reconfiguration of a Multi-oscillator Network by Light in the Drosophila Circadian Clock. Curr Biol 28, 2007-2017. Doi: 10.1016/j.cub.2018.04.064

> Saint-Charles, A., Michard-Vanhée, C., Alejevski, F., Chélot, E., Boivin, A., and Rouyer, F. (2016). Four of the six Drosophila rhodopsin-expressing photoreceptors can mediate circadian entrainment in low light. J Comp Neurol 524, 2828-2844. Doi: 10.1002/cne.23994

> Andreazza, S., Bouleau, S., Martin, B., Lamouroux, A., Ponien, P., Papin, C., Chélot, E., Jacquet, E., and Rouyer, F. (2015). Daytime CLOCK Dephosphorylation Is Controlled by STRIPAK Complexes in Drosophila. Cell Rep 11, 1266-1279. Doi: 10.1016/j.celrep.2015.04.033

Team members