Mitosis is one of the fundamental processes in the development of higher organisms. An essential component of mitosis is the formation of a mitotic spindle made of dynamic microtubules that spatially organize and then separate the divided chromosomes. Malfunctioning of the mitotic apparatus can lead to severe pathologies, such as the Down's syndrome. In addition antimitotic drugs, such as taxol, are important in treatment of cancer. Understanding of mitotic spindle morphogenesis is also one of the outstanding problems in the biology: this phenomenon can be viewed as a prototype for the study of assembly of cellular structures. The mitotic apparatus has be to functionally precise, but its assembly is done without a detailed blueprint - the construction of mitotic spindle is thus an example of the """"""""stochastic molecular architecture"""""""" where random molecular processes paly a crucial role. The main goal of this project is thus to study the formation of the asters of microtubules components. the experiments will be performed by means of video-enhanced optical microscopy (fluorescence, differential contrast) and of micromanipulation techniques (optical and magnetic tweezers). The studies will be mainly done in highly simplified, in vitro systems such as Xenopus laevis eggs extracts. A special emphasis will be put on the quantitative aspects of these studies: the experimental data will be compared with the results of theoretical modeling and numerical simulations. Among other specific goals, the present study will try to: (i) determine the main implications of the regulation of microtubule assembly by the cell cycle enzymes (cdc2-cyclin kinases);(ii) investigate the consequences of diffusion limited growth, e.g. the possibility of depletion regions near the centrosomes which can alter the assembly process; (iii) search for sustained gradients of regulation enzymes, which might provide the cell with spatial morphological information necessary to build the spindle; (iv) determine the mechanisms of aster centering.
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