Type of contract CDD
Location Lyon, France
Statut Available
Key Words
Details of the offer
Sleep disruption is strongly and bidirectionally associated with cardiometabolic diseases, yet the mechanisms linking sleep/wake defects to these pathologies remain poorly understood. We hypothesize that modulation of the transport and utilization of branched-chain amino acids (BCAAs) in the brain across the sleep/wake cycle represents a key mechanistic link. BCAAs are essential amino acids central to insulin and TOR signaling and, in the brain, participate in the glutamate/GABA/glutamine cycle, thereby influencing the excitatory/inhibitory balance. Their cellular uptake, including transport across the blood-brain barrier, depends on the large neutral amino acid transporter LAT-1, where BCAAs compete with monoamine precursors such as phenylalanine, tryptophan, histidine, and tyrosine, potentially impacting monoaminergic neurotransmission. Our published and recent work in Drosophila demonstrates that BCAA transport modulates the activity of specific GABAergic and dopaminergic neuronal subpopulations and affects the sleep/wake cycle. Together, these data indicate that free BCAA levels are regulated by clock- and sleep/wake-dependent metabolic interactions that ultimately shape the activity of selective neuronal circuits involved in sleep regulation.
The goal of this project is to exploit the experimental flexibility of Drosophila to elucidate how BCAAs shape the sleep/wake cycle through inter-organ communication, via four aims: (1) monitor BCAA levels in the hemolymph and brain; (2) assess intracellular BCAA levels in GABAergic and dopaminergic neuronal circuits involved in sleep/wake regulation; (3) determine how neuronal activity influences intracellular BCAA levels; and (4) evaluate how BCAA-dependent pathways impact sleep/wake behavior.
We will quantify hemolymph and brain BCAA levels in individual flies while manipulating sleep and the circadian clock to define their relationship with sleep/wake states. Leveraging the adult brain connectome and powerful genetic tools in Drosophila, we will identify sleep-regulatory GABAergic and dopaminergic neuronal subsets sensitive to BCAA transport and metabolism. Neuronal activity will be monitored using calcium imaging, and intracellular BCAA levels will be measured with a newly developed biosensor, providing mechanistic insight into metabolic control of sleep.
The project will involve the collaboration and continuous interactions between the team of Laurent Seugnet focused on sleep molecular genetics in Drosophila, the neurochemistry facility headed by Sandrine Parrot, both in Lyon, France, and the team of Thomas Riemensperger in Cologne, Germany, which has expertise in connectomics and Drosophila monoaminergic neurons. The project is funded by ANR and DFG and provides two PhD positions (one in France and one in Germany) to carry out complementary aspects of the research program.
The student will receive training in state-of-the-art approaches in advanced HPLC techniques used in neurochemistry, drosophila molecular genetics and neurobiology, behavioral analysis of sleep, and microscopy imaging (confocal, FRET).
Research environment: The student will be part of the WAKING team dedicated to unravel the mechanisms of sleep/wake regulation and associated pathologies, combining both basic research in Drosophila, mice models, and human as well as epidemiological and clinical studies. The student will also be integrated in the NeuroDialyTics facility, specialized in the collection, handling and analysis of neuroactive compounds present in very low-volume samples collected for experimental research. The CRNL (https://www.crnl.fr/fr/page-base/presentation-crnl) is a large (24 teams, 10 facilities, >450 members) interdisciplinary research institute dedicated to translational research in virtually all areas of neuroscience.
Type of job
Type of contract CDD
Application deadline
Employment start date 16/12/2026
Contact
laurent.seugnet@inserm.fr
sandrine.parrot@univ-lyon1.fr