The project "NEMO" is organized around four main work packages (WP) combining molecular, cellular and physiological approaches. The project is built with sufficiently independent work packages and tasks to not jeopardize one another’s success.
This research program has four main objectives:
WP1 - The characterization of the whole repertoire of both the neuropeptides and G Protein-coupled receptors (GPCRs) expressed in selected marine organisms (eels, oyster, cuttlefish, coral) of evolutionary, economic and environmental importance via in silico mining of their transcriptomes and /or genomes combined to a high throughput mass spectrometry approach. This WP will generate completely new information concerning the diversity of mature neuropeptides and GPCRs in distant animal models.
WP2 - Gaining insight into the evolutionary history of neuropeptide and receptor super-families in metazoans. To address this goal, we will undertake phylogenetic and synteny analyses using the different data sets available or generated in WP1. This should help infer evolutionary scenarii of GPCR and neuropeptide super-families in bilaterians as well as, with the integration of cnidarian data, the identification of ancestral GPCR and neuropeptide families in metazoa
WP3 - Functional characterization of neuropeptide / receptor pairs in marine models. In this WP we will address the question of the functionality of the neuropeptides and the way they activate their target cells. Actual ligand /receptor pair interactions will be investigated via the development of a reverse pharmacology assay. In parallel, the tridimensional structure of highly purified candidate peptides in association with SUVs (small unilamellar vesicles) will be studied using NMR.
WP4 - Physiological role of neuroendocrine pathways in reproduction and adaptation to global changes in non-conventional marine models. Investigation will include in vitro experiments (primary cell cultures and tissue explants…), in vivo experiments in aquarium facilities of the partner Institutions, as well as field studies, in order to assess the role of selected neuropeptides and their receptors in the neuroendocrine control of reproduction, and provide the bases of their responses to environmental factors (focusing on the effects of temperature). This will offer the unique opportunity to engage a wide comparative survey of the roles of neuropeptides in the integration of global changes and their consequence on reproduction and associated regulatory processes in phylogenetically distant animals.