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Accueil > Animation scientifique > Séminaires passés

Séminaire hebdomadaire UGSF - Stéfania Robakiewicz - 25 janvier 2019 - CCHB - Amphithéâtre

SEMINAIRE HEBDOMADAIRE DE L’UGSF

"Mannitou Monoclonal Antibody as a Potential Diagnostic and Therapeutic Tool"

Animé par : Stéfania ROBAKIEWICZ, 3ème année de thèse, sous la direction de Madame BOUCKAERT Julie - Equipe "Biologie systémique moléculaire et computationnelle" de l’UMR 8576 - Université de Lille - CNRS


Résumé :

Mannitou antibody as a potential diagnostic and therapeutic tool

Stefania Robakiewicz1, Sonia Serna2, Begoña Echeverria2, Diego Charro3, Nicola Abrescia3, Sandra Delgado4, Ana Arda4, Niels Reichardt2, Jesús Jiménez-Barbero4, Julie Bouckaert1
1Unité de Glycobiologie Structurale et Fonctionnelle, UMR 8576 du CNRS et Université de Lille, 50 Avenue Halley, 59650 Villeneuve d’Ascq, France ;
2Glycotechnology Laboratory, CICbiomaGUNE, Paseo Miramón 182, 20014 San Sebastian, Spain ;
3 Chemical Glycobiology Lab, CIC bioGUNE, Bizkaia Technology Park, 48160 Derio, Spain ;
4 Structural Virology Lab, CIC bioGUNE, Bizkaia Technology Park, 48160 Derio, Spain.

The importance of glycosylation in physiological and pathophysiological conditions is becoming increasingly recognised.1 Unfortunately, the quick detection of modifications in the expression of glycans associated with pathophysiological conditions is still difficult due to lack of specific tools and markers.2 Mannitou IgM, a monoclonal murine antibody, was characterised as being able to specifically recognise the trimannosyl core structure of N-linked glycans called paucimannose. Up to this point, we have managed to produce Mannitou by means of hybridoma technology as well as transient expression in HEK293T cells. On the paucimannose glycan array, Mannitou exhibits strongest binding to Man3GlcNAc2. Almost any substitution on this structure strongly reduces or even inhibits binding. The unmodified paucimannose N-glycans are expressed abundantly in plants and invertebrates, whereas in healthy mammalian cells they are detectable in only very small amounts. However, they are highly present in numerous human cancer tissues, human adult pancreatic stem cells and inflamed mouse pancreata. The prediction of the Fab structure was done using homology modelling of the variable and constant domains. The Mannitou-paucimannose interactions are being studied by means of SPR, BLI and STD-NMR that provide essential information i.a. on binding kinetics and specificity. Crystallisation is being anticipated. The up-regulation of paucimannose N-glycans under tumourigenic and inflammatory conditions makes the Mannitou antibody a promising diagnostic and therapeutic tool.

References
1. Dahmen A.C., Fergen M.T., Laurini C., Schmitz B., Loke I., Thaysen-Andersen M., Diestel S. 2015 Paucimannosidic glycoepitopes are functionally involved in proliferation of neural progenitor cells in the subventricular zone. Glycobiology, 25 : 869-880.
2. Zipser B., Bello-DeOcampo D., Diestel S., Tai M.H., Schmitz B. 2012. Mannitou monoclonal antibody uniquely recognizes paucimannose, a marker for human cancer, stemness, and inflammation. Journal of Carbohydrate Chemistry, 31 : 504–518.


Le vendredi 25 janvier 2019 à 11h00 au CCHB - Amphithéâtre.