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For high fidelity chromosome segregation, kinetochores must be captured properly on the mitotic spindle before anaphase onset. According to the "search and capture" model, the microtubules nucleate in a random direction, grow and shrink dynamically to probe space, and eventually encounter target kinetochores. Thanks to simulation, we try to better understand this mitotic phase and its counterpart in prokaryotic cells during plasmid segregation.
Chromatin plays a key role in spindle assembly: it activates signaling pathways that modify cytoplasm locally such that it promotes microtubule growth. We study the role of chromatin mass and geometry in spindle formation and organization using novel, DNA-bead microcontact printing technique. This technique allows us to pattern DNA beads into various mesoscopic shapes. We incubate the patterns containing different DNA-bead shapes in Xenopus laevis egg extracts and follow spindle assembly dynamics using fluorescence confocal microscopy. Our findings suggest that the chromatin mass and geometry control microtubule concentration and organization during mitotic spindle formation.
Its tractable cylindrical shape, amenable genetics and cell cycle regulated growth patterns make fission yeast an excellent model organism for the studies of morphogenesis and polarity establishment. I am interested in the interplay between microtubules and cell shape. To this end, I am perturbing the normal rod shape of fission yeast with microtubule depolymerizing drugs and I am observing the growth zone localization, the generation of abnormal shape and the subsequent microtubule organization. Our goal is to combine this data with computer models to simulate morphogenesis in fission yeast.
Our long-term research objective is to understand cytoskeletal organization in living cells, with an emphasis on mitosis. We develop in-vitro assays, quantitative image analysis and cytosim, a computer simulation to study cellular architecture from a mechanistic perspective, modeling the interactions of fibers and associated proteins such as molecular motors.
Spindle assembly on micropatterned DNA beads attached onto microscopes slides has recently been developed in the lab. Now it's time to focus on post-processing of the acquired data. From each experiment, a large amount of data is collected. Writing macros helps us to automates and speed up the data analysis. The characterisation of the spindle dynamics according to the DNA pattern will give us information on their behaviour and helps us on the interpretation of future experiments. As new patterns need to be engineered for the experiments and our knowledge grows, we are developing a more flexible way to print micropatterns. I collaborate with Celine, Ana and Francois to extract the information from these experiments and imagine new patterns.
Microtubules, motor complexes (Ncd and Eg5-like) and many lines of C++ are the ingredients of my project. I mix and shake them in order to investigate metaphase spindles in a computational approach. Running several thousand simulations with slightly different starting conditions and analyzing them allows me to screen for good parameter sets. These are used to model a fully dynamic model of metaphase spindles that are eventually aligned depending on cortical cues during mitosis. Using these basics I want to model multipolar centrosome fusions in HeLa cells.
One of the oldest and most important questions in biology is how life organises itself into forms that are both very precise in the sense that they are repeatable but also general in the sense that a huge variety of forms can be generated by subtle changes in the organization of the component parts. The fundamental unit of life is the cell and is a natural starting point for investigating this question. My research is focussed at understanding how the cytoskeleton directs changes in cell shape during the life cycle of the model eukaryotic organism S. pombe.