DYSCO - Dystrophin-associated protein complex and subcellular compartmentalization
Our project with the team of Vincent Mirouse
(iGred, Clermont-Ferrand) and Helge Amthor (UVSQ)
has been selected by ANR ! The Dystrophin Associated Protein Complex (DAPC) is a key actor of the cell – extracellular matrix (ECM) interface, as revealed by its implication in human genetic disorders. However, its molecular and cellular functions are still poorly understood because tractable model systems allowing state-of-the-art in vivo cell biology and genetic approaches are lacking. Our three teams have developed the first transgenic dystrophin reporters that have revealed remarkably compartmentalized membrane distributions of the DAPC in epithelia and muscle cells in C. elegans
, Drosophila, and mouse. The project aims to elucidate the organization and dynamics of the DAPC and to characterize its new functions in relation to specific cell cortical compartments.
NERVSPAN - Molecular plasticity of neurons during C. elegans lifespan
2023-06 - Marie Skłodowska-Curie Actions - European Training Network
Within the framework of the NERVSPAN European Doctoral Training Network, we are offering a fully-funded PhD fellowship to study the robustness of neuronal excitability and function across gender and lifespan.
The intrinsic electrical properties of neurons are defined by the repertoire of ion channels they express. Determining the precise genetic programs that establish the electrical identity of neurons remains a major question in cellular neuroscience. Single-cell transcriptomic studies in the C. elegans nervous system have revealed that potassium channels are often expressed in complex combinations of over a dozen channel genes in a single neuron. These different ion channel combinations will determine the biophysical and electrical properties defining neuron-specific functions throughout its life.
From a conceptual point of view, this project will address for the first time how ion channel degeneracy, variability and covariation are genetically regulated to ensure the resilience and phenotypic stability/plasticity of excitable cells in C. elegans.
NERVSPAN will train 11 doctoral Students at 7 academic institutions and 2 companies. The nature of the programme will provide the enrolled students with strong interdisciplinary training (including, but not limited to: molecular biology, bioinformatics, high resolution microscopy, proteomics, and transcriptome profiling).
Find more information here.
Paper Alert - Distinct dystrophin and Wnt/Ror-dependent pathways establish planar-polarized membrane compartments in C. elegans muscles
Our study revealing the remarkably complex organisation of the worm's sarcolemma is now on BioRxiv!
Four and half years in the making, congratulations to Alice, Nora, Marie, Amandine, Noémie and Olga for this magnum opus
revealing this entirely unsuspected new case of planar cell polarity
in C. elegans
The plasma membrane of excitable cells is highly structured and molecular scaffolds recruit proteins to specific membrane compartments. Here, we show that potassium channels and proteins belonging to the dystrophin-associated protein complex define multiple types of planar-polarized membrane compartments at the surface of C. elegans muscle cells. Surprisingly, conserved planar cell polarity proteins are not required for this process. However, we implicate a Wnt signaling module involving the Wnt ligand EGL-20, the Wnt receptor CAM-1, and the intracellular effector DSH-1/disheveled in the formation of this cell polarity pattern. Moreover, using time-resolved and tissue-specific protein degradation, we demonstrate that muscle cell polarity is a dynamic state, requiring continued presence of DSH-1 throughout post-embryonic life. Our results reveal the intricate, highly reproducible, and entirely unsuspected complexity of the worm's sarcolemma. This novel case of planar cell polarity in a tractable genetic model organism may provide valuable insight into the molecular and cellular mechanisms that regulate cellular organization, allowing specific functions to be compartmentalized within distinct plasma membrane domains.
Fleggsibility - Dissecting the microevolutionary flexibility of a neural circuit
Our project with the team of Christian Braendle
(iBV Nice) and ViewPoint: Behavior Analysis Technologies
has been selected by ANR ! On the heals of our joint publication (Vigne et al., Science Advances 2021
) we will be trying to understand how specific neural circuits evolve to generate natural behavioural variation within species. In particular, the precise genetic changes that modulate cellular and developmental architectures of reproductive systems remain unclear. Here we will focus on the simple egg-laying circuit of the nematode Caenorhabditis elegans
as a powerful model system to study natural microevolutionary (intraspecific) variability.