Molecular Dynamic of Neurons during C. elegans Lifespan

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The objective of this network is to train, through research, a group of 10 young scientists, giving them the practical skills and knowledge necessary to tackleThe function of a neuron is determined by its expression of morphogen receptors and adhesion proteins (to pattern its connectome), of synaptic protein complexes (for intercellular communication), and of ion channels (for neuronal excitability and signal propagation). The protein composition of any neuron is itself dependent on gene expression controlled by transcription factors and by post-transcriptional regulations (splicing, translation, protein stability). Finally, neurons are highly compartmentalized cells and require trafficking of proteins to their correct locations. Alterations of these neuronal features can therefore be observed at multiple levels: molecular, cellular, and behavioral. We will focus on three neuronal features: i) gene expression levels as measured by RNA sequencing and proteomics, ii) assembly of functional multiprotein complexes (by high resolution microscopy and proximity dependent protein labelling), and iii) phenotypic output via a combination of optogenetics, calcium imaging, and behavioral assays.This research program will help define the critical features that differentiate between physiological and pathological states of a given neuron. Such biomarkers would be precious to facilitate drug screens or develop novel therapeutic strategies for human neurological diseases.The interdisciplinary research and training programme will cover a broad spectrum of approaches and topics, fromintracellular molecular interactions to cell-cell communication, gene expression profiling, the impact of deleterious mutations, behavioral studies, and translation regulation. Coupled with extensive network-wide transferable skills training, this will prepare the fellows for careers in the medically important field of neurobiology as well as a broad range of carriers including government and industry.