We are interested in the molecular mechanisms governing asymmetric stem cell divisions, with emphasis on the role of the mitotic orientation in determining daughter cells' fate. The proper execution of asymmetric divisions is crucial in generating tissue diversity during development, and for tissue homeostasis and regeneration in adult organisms. Failures in asymmetric divisions cause abnormal proliferation, and correlated with cancer progression (Santoro, EMBO Rep. 2016).
To make a cell division asymmetric, the orientation of the mitotic spindle has to be tightly coordinated to cellular polarity. This way, daughter cells are properly positioned within the tissue, inherit unequal sets of fate determinants and follow differential fates. This observation sets the stage for our studies, aimed at gaining insight into the functional and organisational principles of the molecular machines orchestrating asymmetric cell divisions. To address this biological problem, we use a combination of high-resolution X-ray crystallography, biochemical analyses on reconstituted protein complexes and stem cell biology. Our activity is organized in three main research lines: