ÁLVARO TAVARES

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The underlying theme behind the work of our laboratory is to study the basic biology of mitotic cell division, in particular the aspects regulating the formation of a bipolar mitotic spindle and the connection between centrosomes and cytokinesis. The ultimate goal is to understand how modifications of these processes contribute to the transformation of normal into cancer cells. 

PosDoc and PhD positions at the bottom of the page

LATEST RESEARCH

Knockdown of one of our kinetochore genes. Chromosome fails to align during metaphase and cell goes into apoptosis.

Cytokinesis failure and regression

We have recently found that SGT1, a highly conserved  protein, is required for Polo protein stability and  kinetochore assembly. Sgt1 has been found to associate with the molecular chaperone HSP90, and the Skp1 subunit of SCF (E3 ubiquitin ligase). We found Sgt1 to be required for proper centrosome maturation and mitotic spindle assembly in mitosis. Mutant analysis show that Sgt1 is an essencial gene, and lack of Sgt1 results in block in a prometaphase/metaphase stage due to activation of the spindle assembly checkpoint. However, we found that most mutant neuroblasts dont ever reach mitosis due to the activation of the DNA damage checkpoint. Moreover, lack of Sgt1 severely compromises spindle assembly, centrosome maturation and centrosome number. Importantly, we show that protein levels of several centrosomal components, including Polo and g-tubulin, are severely  reduced in the Sgt1 mutant.

IDENTIFICATION AND CHARACTERIZATION OF MITOTIC KINETOCHORE PROTEINS. We have developed a new method to obtain enriched mitotic kinetochore preparations  from Drosophila embryos and cultured cells. This way we have identified 92 proteins of which 26 correspond to previously uncharacterized genes.  Expression of these proteins as GFP-fusions in cultured cells, showed that 10 do accumulate on the mitotic kinetochores. In addition, their downregulation by RNAi  results in severe  chromosome congression and segregation defects. In agreement with these results, preliminary mutant analysis for four of new  genes show that they are essential in early embryonic or larval development. Finally, we have identified the human homologues for some of the new genes and downregulation of these in HeLa cells also resulted in severely defective chromosome congression and segregation during mitosis. 

UPCOMING EVENTS

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Dynamic kinetochore EMBO Workshop

Oslo, Norway

June, 28- July 1, 2022

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Chromosome segregation and aneuploidy
May 1-4, 2022 

We are looking for Post-Docs and PhD students