Dynamic instability of microtubules and effect of microtubule targeting agents – Ayuna Barlukova

Ayuna Barlukova
I2M, Aix-Marseille Université

Date(s) : 21/03/2017   iCal
10 h 30 min - 12 h 30 min

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


Lien : theses.fr


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