University of Dundee

4 Year Wellcome Trust PhD Programme: Mechanisms of asymmetric stem cell division

Despite tremendous progress the origin of cancer is still a matter of debate for many malignancies, but it is clear that stem cells play an important part in this context. How are stem cells and the onset of tumorigenesis linked? Some stem cells can divide asymmetrically. This means that when they divide the stem cells self-renew and at the same time produce a daughter cell that will have another fate. If this process of cell fate assignment by asymmetric stem cell division goes wrong, tumourigenesis can be triggered. So how does the process of asymmetric cell division protect stem cells from forming tumours? In order to answer this question, we need to understand how asymmetric stem cell division is controlled normally.

The project will use neural stem cells of the developing nervous system of the fruit fly as a model system to interrogate the molecular mechanisms of asymmetric cell fate generating stem cell divisions. It will in particular focus on the analysis of how the evolutionarily conserved partitioning-defective (PAR) complex regulates the actomyosin cytoskeleton during asymmetric cell division of these neural stem cells. Using chemical-genetics and super resolution real time confocal microscopy, the project will explore how the PAR complex and the actomyosin network act in concert over time to allow asymmetric cell division.  This involves the use of CrispR/Cas9 to edit the genome to generate new tools as well as optogenetic approaches in combination with nanobody expression to manipulate the subcellular localization of endogenous molecules within the stem cells to reveal the temporal and spatial function of key polarity proteins to build better models of how asymmetric division of stem cells is controlled to prevent the lineage to proliferate out of control.