UNDERSTANDING MICROTUBULE DEPENDENT SIGNALLING IN THE GENERATION OF CELLULAR ASYMMETRIES
Most animal cells are polarized; they show structural and functional differences across the cell. Cell polarity is essential for the generation of asymmetric divisions, cellular movements and for cells to organize into complex structures such as organs. Dysregulation of cell polarity can cause developmental disorders, including different types of cancer. Therefore it is important to understand the molecular mechanism that establish and maintain cell polarity.
The cellular cytoskeleton is involved in the asymmetric distribution of proteins that orchestrate cell polarity. The molecular mechanisms through which the cytoskeleton and in particular microtubules (MT) regulate polarity proteins remains elusive. As a step towards understanding these mechanisms, in previous research we have identified the most comprehensive network of polarity regulator candidates to date (Nat Cell Biol 2012 vol.15(1) pp.103-12). This network currently informs our design of genetic screens in C. elegans, which are successfully identifying novel MT dependent polarity regulators in asymmetric cell division. We are using state-of-the-art genetic, biochemical, molecular, live cell-micromanipulation and imaging techniques to determine the cell polarity role of the identified genes. In addition, we want to extrapolate our findings to mammalian cells using in vitro culture systems were we can observe live asymmetrically dividing cells. Our ultimate goal is to understand the role of the identified polarity regulators in a whole organism context during morphogenetic movements and tissue organisation.
Start Lab in 2015