Control of stem cell fate by cytoskeletal motors during asymmetric cell division
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Asymmetric cell division is the process by which one cell divides into two daughter cells that have different fates, and it gives rise to the plethora of cell types found in an organism. Asymmetric cell division is a hallmark of stem cells, and failure in this process has been linked to tumor formation and ageing.
We are interested in understanding the molecular and physical mechanisms underlying asymmetric cell fate determination during asymmetric cell division. In particular, we recently discovered a novel mechanism of asymmetric dispatch of fate determinants in Drosophila Sensory Organ Precursors. In these cells, the central spindle, the antiparallel array of microtubules characteristic of late mitosis, is asymmetric. This spindle asymmetry is in turn “read” by a molecular motor, the kinesin Klp98A, to carry endosomes containing cell fate determinants into only one of the two daughter cells.
This project aims at understanding how Klp98A physically “reads” the asymmetry of the central spindle to drive polarized traffic. Using micropatterning technology, the successful applicant will reconstitute an asymmetric central spindle in vitro, where features such as microtubule density, polarity, geometry and/or bundling are combinatorially controlled. This controlled microtubule landscape will then be used to investigate the motility and emergent behavior of purified motors, both at the single molecule level or collectively on liposomes. Coupled with physical theory and structural studies Klp98A, this approach will provide a quantitative molecular understanding of polarized trafficking/signaling during asymmetric cell division.
The ultimate goal of this project is to develop a universal theory that could apply beyond asymmetric division to explain polarized traffic in other antiparallel microtubule arrays, such as dendrites.
This project offers a key opportunity to learn a multidisciplinary approach combining in vitro reconstitutions and single molecule imaging with quantitative live imaging of trafficking in the developing Drosophila, relying on theoretical physics to bridge these different scales.
Derivery E, Seum C, Daeden A, Loubéry S, Holtzer L, Jülicher F, Gonzalez-Gaitan M. (2015)
Polarized endosome dynamics by spindle asymmetry during asymmetric cell division. Nature. 528 (7581):280-285