Institut de Mathématiques de Marseille, UMR 7373


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Dynamic instability of microtubules and effect of microtubule targeting agents

Mardi 21 mars 2017 10:30-12:30 - Ayuna BARLUKOVA - I2M, Marseille

Dynamic instability of microtubules and effect of microtubule targeting agents

Résumé : Soutenance de thèse
Modélisation d’instabilité dynamique des microtubules et l’effet des agents antimicrotubules
The aim of this thesis is to design new mathematical models that are able to appropriately describe dynamic instability of a population of microtubules (MTs) and effect of drugs on MT dynamics. MT dynamic instability play an important role in the processes of mitosis and cell migration and, thus, in cancer progression. Dynamic instability is a complex process that involves different states of tubulin (polymerized or non-polymerized, GTP-tubulin or GDP-tubulin that correspond to two different energetic states of tubulin dimers) that resulted from chemical processes (polymerization, depolymerization, hydrolysis, recycling, nucleation) linking these different states of tubulin. Description of this complexity by mathematical models enables one to test biological hypotheses concerning the impact of each process and action of drugs on microtubule dynamics. Recent observations show that MT dynamics depends on aging of MT. One of the aims of the work is to test the hypothesis that MT aging results from the acceleration of the GTP hydrolysis. We construct for that new models that couple two multidimensional transport equations with two ordinary differential equations involving integral terms. We have calibrated our models on the basis of experimental data ; tested biological hypothesis on mechanism of aging process ; performed a sensitivity analysis of the model with respect to parameters describing chemical processes ; and tested hypotheses concerning actions of drugs.
Membres du jury :
- Assia BENABDALLAH, PU, Aix-Marseille Universite, Examinateur
- Francois DEVRED, MCF - HDR, Aix-Marseille Universite, Examinateur
- Stéphane HONORÉ, PU-PH, Aix-Marseille Universite, Codirecteur
- Florence HUBERT, PU, Aix-Marseille Universite, Directrice
- Clair POIGNARD, CR1 - HDR, INRIA Bordeaux Sud Ouest, Rapporteur
- Christian POÜS, PU-PH, Châtenay-Malabry, Rapporteur
- Magali RIBOT, PU, Université d’Orleans, Examinateur
- Angélique STEPHANOU, CR CNRS - HDR, TIMC Grenoble, Examinateur

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Lieu : FRUMAM (deuxième étage) - Aix-Marseille Université - Site St Charles
3, place Victor Hugo - case 39
13331 MARSEILLE Cedex 03

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