Caractérisation de la diversité moléculaire des venins de cônes de Mayotte et de la Polynésie française

Cone snails are marine mollusks belonging to the Conidae family. Cones are carnivorous species which are capable to produce and inject a paralytic venom to prey and defend themselves. They can be classified into three main categories based on their diet, being piscivorous, molluscivorous or vermivorous. Their venom is secreted inside a specialized venom gland, known to produce diverse toxins. Venom's ability to paralyze is attributed to the synergic activity of different conotoxins during a sting. Recently, it has established that cones can adjust their venoms' molecular content depending on the state they are in: predatory or defensive. Conotoxins are interesting tools to study biological receptors and the complex mechanisms involved, and are a rich source of potential therapies. The research project consists in the molecular characterization of cone snail venoms from Mayotte (Indian Ocean) and French Polynesia (Pacific Ocean). The main objective was to characterize the venom profiles of different species by mass spectrometry coupled with liquid chromatography (LC-MS), integrated with proteo-transcriptomics to characterize the entire venom of a cone species. The procedure was applied to characterize the venom of three different cones: C. canonicus (molluscivorous), T. bullatus and G. obscurus (piscivorous). First, predatory and defensive venoms were analyzed through LC-MS to evaluate the complexity of each venom injections. Then, the same venoms were analyzed through a bottom-up proteomic strategy. The different analyses have allowed to highlight, not only, significant interspecific venom diversity between the three cones, but also a remarkable intraspecific venom diversity (between different injections of the same cone). This study has allowed to confirm the selection of different toxins superfamilies to achieve different purposes, to ensure their survival. Indeed, in each predatory or defensive venoms, different set of conopeptide superfamilies are injected. They also include different proteins and enzymes which are assumed to catalyze post-translational modifications known to strongly help improve venom efficacy. Overall, each venom injection contained high levels of the O, A and M gene superfamilies, which are assumed to be essential for cone' survival. Further works would be interesting in order to quantify and characterize the biological mechanisms of toxins. It would also be important to uncover the tridimensional structure and biological target for each.