Eleven young researchers addressed cell division from a different perspective using complementary techniques, approaches and experimental model systems. Ivan, Jijumon., Evi and Pragya studied tubulin post-translational modifications. Using human tissue culture cells and zebra fish embryos Ivan found that spindle microtubule polygltuamylation is essential for faithful chromosome segregation during mitosis. Jijumon managed to purify, tubulin from mammalian cell lines with a set of precisely defined posttranslational modifications, and directly measure how these modifications control the interactions with a panel of microtubule-associated proteins. Evi focused on the enzymes that create tubulin posttranslational modifications in the meiotic spindle of human oocytes finding specific differences in expression between oocytes cultured in vitro and matured in vivo. Pragya aimed at identifying inhibitors of Tubulin Tyrosine Ligase Like (TTLL) 4, an enzyme, that polyglutamylates tubulin a modification involved in neuronal maturation and metastatic progression. She managed to set up a novel pipeline for High Throughput Screening of TTLLs identifying and validating small molecule inhibitors of a chemical compound library comprising 190.000 compounds.
Christel, Ennio and Alejandra studied the topology of protein assemblies within the spindle. Christel successfully purified some of the main human components of the dynein complex to perform in vitro experiments of spindle assembly. Ennio purified Dynactin subcomplexes to study the silencing of Spindle Assembly Checkpoint, and studied the crucial role of the putative adaptor and cargo binding protein Spindly in this process. Alejandra studied the mechanisms regulating minus-end dynamics of spindle microtubules focusing on the characterization of a recently identified protein complex that associates specifically with the K-fiber microtubule minus-end during mitosis. In collaboration with Robert visualised through tomography how this complex alters K-fibers of spindles assembled in silenced cells.
Ana, Robert, Manuel, and Pablo focused on the visualization and the quantitative analysis of cell division. While studying the differences between meiosis and mitosis in the spindle dynamics and chromosome segregation, Ana found the proteins responsible for spindle elongation during meiosis. Robert obtained the first full 3D reconstructions of metaphase and anaphase spindles in a human cell line. These reconstructions are complemented by detailed quantitative descriptions of microtubule organization within these spindles. Manuel used mathematical modelling to explain how motor proteins, dynamic filaments, and microtubules assemble to form an elongating spindle. He found why longer spindles elongate faster. Pablo developed a microfluidic device based on the Cherry Temp device that allows thermalizing and perfusing with different buffers a cell sample in the microscope. Further, Pablo started to develop an Artificial Intelligence based classifier to better predict the effect of specific targets on the cell decision.
As a main training and dissemination activity, the DivIDE fellows organized the conference “From Pole to Pole” in Barcelona. The fellows that were located hundreds of kilometres away across Europe had to team up to decide on the scientific content and the speakers list, as well as establish the needed logistics, the budgeting of expenses, scouting for sponsors and outreaching the event to manage the conference etc. This was an intensive learning process during the months prior to this event and also during the event itself. The conference was a big success and all fellows acknowledged that the event was mind opening.
