Group Leader
Hélder Maiato

 

Our group is interested in understanding how mitosis works from a mechanistic standpoint and how mitotic failure may lead to aneuploidy, contributing for a better understanding of how cancer arises and how it could be treated. Specifically, we are focusing on the mechanisms of force production necessary to move chromosomes during mitosis, paying particular attention to the structural and molecular requirements behind mitotic spindle assembly and function.

Our studies on the mitotic roles of the microtubule plus-end tracking proteins (+TIPs) CLASPs helped providing a molecular explanation for the MT-based motility of chromosomes during mitosis. CLASPs participate in and are required to maintain spindle architecture by playing an essential role in spindle MT flux, whose role is being intensively studied in the lab.
We also demonstrated that kinetochores can organize their own MTs, contributing for spindle morphogenesis in animal cells. This mechanism appears to be fundamental not only for the assembly of acentrosomal spindles, as occurs in all higher plants and some animal meiotic cells, but is also present in cells that normally have centrosomes.

In addition to already identified candidates, we are currently performing genome-wide RNAi screens of genes required for specific pathways of spindle assembly, which we aim to characterize from a functional perspective. For this purpose we employ proteomic and molecular biology methods, combined with state-of-the-art live-cell microscopy techniques, such as Fluorescent Speckle Microscopy and Laser Microsurgery, to interfere with gene, protein or structure function in living cells, using Drosophila and mammalian culture cells as model systems. In parallel, we plan on exploring a possible link between cell division and cancer by investigating the contribution of specific molecules required for mitosis using in vivo mammalian model systems.