C. elegans synapse neuromuscular junction GABA receptors Acetylcholine receptors aging genetics molecular neurobiology electrophysiology optogenetics super resolution microscopy electron microscopy
Synapses are sophisticated nanomachines that support transfer and processing of information between excitable cells. Since most neurons receive thousands of synaptic inputs, the neuronal membrane is a mosaic of specialized microdomains where neurotransmitter receptors cluster in register with the corresponding presynaptic neurotransmitter release sites. Our lab is interested in identifying the cellular and molecular mechanisms involved in the organization and maintenance of the synapse with a specific focus on the control of neurotransmitter receptor expression and localization.
Our strategy is based on the combination of genetics, imaging, electrophysiology and biochemistry in the nematode Caenorhabditis elegans (for more information on C. elegans see “an overview of the model organism C. elegans“). Using the neuromuscular synapse as a model synapse, we identified several new genes involved in the clustering of acetylcholine and GABAA receptors through previously undescribed mechanisms, including a novel anterograde synaptic organizer that assembles extracellular scaffolds in the synaptic cleft. We are currently analyzing the organization, dynamics and maintenance of these synaptic scaffolds as well as the genes involved in the biosynthesis and trafficking of the receptors.
Our results should contribute to a better understanding of the normal and pathological synapse. Specifically, synaptic defects have been involved over the last years in the pathogenesis of a growing number of neuropsychiatric diseases, leading to the concept of “synaptopathies”. However, a number of genes linked to neuropsychiatric diseases have no assigned function, and it is likely that the mutational landscape of these diseases will be complexified by the wealth of data generated with next generation sequencing techniques. Simple organisms should help!
We have currently no funded position but we are always looking for talented and highly motivated students or postdocs.
Institut NeuroMyoGène UCBL – CNRS UMR 5310
INSERM U1217 Faculté de Médecine et de Pharmacie
3ème étage – Aile D
8 avenue Rockefeller 69008 Lyon France