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Multiresistances and Pathogeny factors from Nematodes

The Loire Valley Research Center (UMR 1282 - ISP) focuses on identifying molecular targets and mechanisms of anthelmintic resistance in nematodes. They explore ion channel diversity, validate novel anthelmintic targets, and utilize gene silencing and CRISPR-Cas9 technology. Current research includes identifying resistance markers and conducting Automated Larval Migration Assays on various nematode species. Researchers aim to enhance anthelmintic susceptibility monitoring and validate parasite-specific molecular targets for future anthelmintics.

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Multiresistances and Pathogeny factors from Nematodes

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  1. Loire Valley Research Center UMR 1282 - ISP Multiresistances and Pathogeny factors from Nematodes

  2. Our main research topics Identification of the molecular targets of AH () in nematodes old and new molecules Decipher the molecular mechanisms involved in AH resistance Identify resistance markers Explore the diversity of ion channels from parasitic nematodes: Select and validate novel targets for next generation anthelmintics (chemical or natural) Claude CHARVET (IE, PhD) Jacques CORTET (TR) Guillaume SALLE (IR, DVM, PhD) Elise COURTOT (IE, PhD) Fabrice GUEGNARD (AI) Abdallah HARMACHE (IR, PhD) Christine KOCH (TR) Cedric NEVEU (DR, PhD, HDR) Delphine SERREAU (AT) Nicolas LAMASSIAUDE PhD student Mohamed ISSOUF Post-Doc

  3. Focus on recent technological developments Automated larval migration assay (ALMA) H. contortus L2/L3 ; T. cir; T. col, O. den Heligmosomoides in progress. Gene silencing of AH receptors in H. contortus C. elegans: Expression of parasite specific AH targets Crispr Cas9 : replace native AH targets by their parasitic nematode counterpart

  4. AutomatedLarvalMigration Assay KOK WEY WEY KOK Charvet et al. (in reviewing) Monotoring AH susceptibility or resistance in H. contortus L3

  5. RNAi targeting acetylcholine receptor subunits UNC-29 UNC-29 UNC-38 UNC-38 ACR-8 Unc-38 UNC-29 UNC-29 UNC-38 UNC-38 Blanchard et al. 2018 PLoS Pathogens Validate molecular AH targets in the parasite Hco-L-AChR-1 Levamisole Hco-L-AChR-2 Pyrantel

  6. Expression of parasite « specific » AH targets 26 LEV-1 26 27 UNC-38 LEV-8 27 26 UNC-29 UNC-63 M-AChR Specific to animal parasitic ematodes Courtot et al. 2015 PLoS Pathogens Investigation of parasite AH targets at the subunit level ACh Mor Oxa Lev Beph Nic ACR-8 parasite 100nA 20s Cel- L-AChR Blanchard et al. 2018 PLoS Pathogens

  7. CRISPR Cas9-Mediated acr-16 ORF replacement with parasitic nematode orthologs. mcherry coding sequence as a «visual» exemple RiboNucleoProtein (RNP) = Cas9 + sgRNA

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