Microtubules (MTs) are essential skeletal components of eukaryotic cells.
Indeed, MTs are mainly used as a support for the transport functions of molecules and organelles (Cargoes). This transport of cargoes within cells is carried out by molecular motors, such as kinesin, which have the ability to move these cargoes along the MTs using ATP as an energy source. In humans several genetic diseases (spastic paraplegia) are linked to mutations that affect microtubular transport.
The entire microtubule network is abruptly rearranged during the cell division phase (mitosis) to form a bipolar spindle structure that allows the chromosomes in the two daughter cells to attach and segregate faithfully. The function of the mitotic spindle is not limited to chromosome segregation. Indeed, the orientation of the mitotic spindle of polarized stem cells serves to transmit cell identity information to the daughter cells. The mitotic spindle orientation, when compromised, leads to cell identity defects and tumour formation. Thus, abnormalities in the assembly of the mitotic spindle can lead to (1) defective chromosome segregation (aneuploidy) and (2) cell identity abnormalities, both of which can lead to tumour formation.
Our team is trying to answer several key questions:
-how during the interphase, certain cargo transport functions (dependent on Kinesin) are regulated on MTs
-which are the microtubule regulators (protein kinase, MAPs) that orchestrate the timing, assembly and rapid reorganization of MTs during mitosis
-how, at the tissue level, tissues develop where asymmetric stem cell division has been compromised
To answer these questions, we use a combination of cutting-edge biochemical, proteomic, genetic and microscopic approaches with fruit flies and human cells in culture as model systems.
Keywords: microtubule, transport, cell division, chromosome, stem cell, tumor