Dynamic instability of microtubules and effect of microtubule targeting agents

Ayuna Barlukova
I2M, Aix-Marseille Université
http://www.lcqb.upmc.fr/users/ayuna-barlukova

Date(s) : 21/03/2017 iCal
10h30 - 12h30

http://www.theses.fr/s110162

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